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(21) Application Number:EfP/2011/001282

(22) Filing Date: 28/09/2009

(30) Priority data: 08018721.4 27/10/2008 EP and 09161388.5 28/05/2009 EP

(86) PCT data PCT/EP09/062525 28/09/2009 W020 I 0/049228 06/05/2010

(73) Owner: SYNGENTA PARTICIPATIONS AG ofSchwarzwaldallee 215, CH-4058 Basel, Switzerland.

(72) Inventor: GIORDANO, Fanny Synenta Crop protection AG, Schwarzwaldallee 215, CH-4058 Basel, Switzerland; GRIBKOV, Denis Syngenta Crop Protection Munchwilen AG, Breitenloh 5, CH-4333 Munchwilen, Switzerland; ANTELMANN, Bjorn, Syngenta Crop Protection Munchwilen AG, Breitenloh 5, CH-4333 Munchwilen, Switzerland; WALTER, Harald; Syngenta Crop Protection Munchwilen AG, Breitenloh 5, CH-4333 Munchwilen, Switzerland. and DE MESMAEKER, Alain; Syngenta Crop Protection Munchwilen AG, Breitenloh 5, CH-4333 Munchwilen, Switzerland.

(74) Agent/address for correspondence: MURIU, MUNGAI & COMPANY ADVOCATES P.O BOX 75362-00200 NAIROBI

(54) Title: PROCESS FOR THE PREPARATION OF BENZONORBORNENES.

(57) Abstract: The present invention relates to a novel a process for the preparation of9- dichloromethylcne-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-ylamine which process comprises a) reacting cyclopentadiene in the presence of a radical initiator and CXCI3, wherein X is chloro or bromo, to a compound of formula II, or aa) reacting cyclopentadiene with CXCI3, wherein X is chloro, in the presence of a metal catalyst to a compound of formula II, wherein X is chi oro, b) reacting the compound of formula II with a base in the presence of an appropriate solvent to the compound of formula III, c) and converting the compound of formula III in the presence of 1,2-dehydro-6- nitrobenzene to the compound of formula IV, and d) hydrogenating the compound of formula IV in the presence of a metal catalyst.

Process for the preparation of benzonorbornenes


The present invention relates to the preparation of 9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-ylamine.

5    The compound 9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-ylamine is a valuable intermediate for the preparation of benzonorbornene fungicides, as described for example in WO 2007/048556.

It is known from WO 2007/048556 to prepare 9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-

10    methano-naphthalen-5-ylamine by

a) reacting the compound of formula A


&cooH (A) io the preooooo of ao alkyl oibile

NH2

with a compound of formula B

15

R" ~ (B) wherein R'and R" are e.g. C1-C4alkyl, to a compound of formula C
R't=V

b) hydrogenating the compound of formula C in the presence of a suitable metal catalyst to a compound of formula D

20

c) ozonising the compound of formula D with subsequent treatment with a reducing agent to a compound of formula E
 
~olE),
N02

d) reacting the compound of formula E triphenylphosphine/carbon tetrachloride to 2,9-dichloromethylidene-5-nitro-benzonorbornene of formula F

~CI

y---"  Cl (F)
N02

5    and

e) hydrogenating the compound of formula F in the presence of a metal catalyst to 9-dichloromethylene-1, 2, 3, 4-tetrahydro-1, 4-methano-naphthalen-5-ylamine.

A disadvantage of this prior art process is the large number of reaction steps which

1 0 decreases the yield of the product. In addition, the ozonolysis reaction which is difficult to handle and the expensive step d) which requires the use of triphenylphosphine makes this process uneconomic and unsuitable for a large-scale production.

The aim of the present invention is therefore to provide a novel process for the production of

15    • 9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-ylamine that avoids the disadvantages of the known process and makes it possible to prepare 9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-ylamine in high yields and good quality in an economically advantageous way with less reaction steps.

20    Thus, according to the present invention, there is provided a process for the preparation of 9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-ylamine of formula I

~CI

~  cl(l),

NH2

which process comprises
 

a) reacting cyclopentadiene with CXCI3, wherein X is chloro or bromo; preferably bromo, in the presence of a radical initiator to a compound of formula II
CCI30--x (II)

wherein X is chloro or bromo,

5    or aa) reacting cyclopentadiene with CXCI3, wherein X is chloro, in the presence of a metal catalyst to a compound of formula II
CCI3
0-x,,J,

wherein X is chloro,

b) reacting the compound of formula II with a base in an appropriate solvent to the

10    compound of formula Ill
Cl6Cl
(Ill),

c) and converting the compound of formula Ill in the presence of 1,2-dehydro-6-nitrobenzene to the compound of formula IV Cl\l

~(IV),

N02

15    and

d) hydrogenating the compound of formula IV with a hydrogen source in the presence of a

metal catalyst.

One embodiment of this process process comprises

20    a) reacting cyclopentadiene with CXCI3, wherein X is chloro or bromo, in the presence of a radical initiator to a compound of formula II
 
CCI3~X (II),


wherein X is chloro or bromo.

Reaction step a) and aa):

5    The compound of formula II can occur in the following isomers or mixtures thereof:

X    X    (lib), 6(lie), (/X (lid), (/X (lie) and erx  (llf),   
A    (lla), ()       
*CI    *CI    ~CI    kCI    -x-CI    ~CI   
Cl   Cl    Cl   Cl    Cl  Cl    Cl  Cl    Cl   Cl    Cl   Cl   

wherein X is chloro or bromo.

The  product of reaction step a) and aa) can be used as it is for the following reaction step

10    b). The isolation or purification of a specific isomer or a isomer mixture of formula II is not necessary. The compound of formula II and its isomers and the compound of formula IV are novel and especially developed for the process according to the invention and therefore constitute a further object of the invention.

15    In principle a large number of radical initiators of following classes can be applied for reaction step a): organic peroxides (for example methyl ethyl ketone peroxide, benzoyl peroxide), organic azo compounds, metal salts and complexes (Cu, Ru). Preferred radical initiators are selected from azobisisobutyronitrile, dibenzoylperoxide and bis(tert-

butylcyclohexyl}peroxydicarbonate. Especially preferred is azobisisobutyronitrile.

20

Reaction step a) is advantageously performed at elevated temperatures, preferably at temperatures of from 20 to 1oo•c, preferably of from 60 to 100 •c, most preferably of from 80 to go•c. The use of bromotrichloromethane is preferred, especially under peroxide or azo compounds initiation.
25

In the especially preferred reaction step aa), cyclopentadiene is reacted with CCI4 in the presence of a metal catalyst to a compound of formula II
 

CCI.3b--x (II),

wherein X is chloro. For step aa), the presence of a radical initiator is not necessary, but can be of advantage to reduce catalyst loading (use of less catalyst).

5    Suitable metals for the catalysts are for example selected from ruthenium, copper, iron, palladium and rhodium. Preferred catalysts contain ruthenium (II) or copper (I) complexes.

Especially preferred catalysts are selected from the group consisting of Ru(PPh3)JCI2, Ru( cumene )PPh3CI2, Ru(Cp )PPh3CI2, Grubbs I (benzylidene-bis(tricyclohexylphosphine )-dichlororuthenium) and CuCI in combination with an amine-ligand, especially a diamine or

10    triamine ligand. Grubbs I, CuCI/tetramethylethylenediamine (TMEDA) or pentamethyldiethylentriamine are the most preferred catalysts.

Reaction step aa) can be performed in the presence of an inert solvent, preferably without a solvent when a Ru-catalyst is used. Reaction step aa) is advantageously performed at

15    elevated temperatures, in particular at temperatures of from 20 to 1oo•c, preferably of from 60 to 100 •c, most preferably of from 60• to ao•c. The product of reaction step aa) is a mixture of the 3 possible isomers. The isolation or purification of a specific isomer or a isomer mixture is not necessary.

20    A preferred embodiment of reaction step aa) can be efficiently performed by heating a mixture of cyclopentadiene with 1.5 to 3, in particular 2 equivalents of carbon tetrachloride in acetonitrile in the presence of 0,5 to 2 mol%, in particular 1 mol% copper I catalyst, preferably CuCI and 1 to 4 mol%, in particular 2 mol% tetramethylethane-1 ,2-diamine

(TMEDA) to give 70-80% isolated yields of product after distillation.

25

Adding of a catalytic amount (usually 1 mol%) of a radical initiator as mentioned above, especially N,N-azobisisobutyronitril to the reaction mixture can reduce catalyst loading (use of less catalyst).

30    Reaction step aa) has further advantages. The use of CCI4 is less expensive, the addition product with carbon tetrachloride (CTCM-cyclopentene) is much more stable than the bromo
derivate (BTCM-cyclopentene), the reaction is much less exothermic and therefore more suitable for large scale production and no bromide anion is generated on the next step.

In reaction step a)  and aa), CCI3Br or CCI4 is used in excess to cyclopentadiene, preferably

S    1.S-S equivalents, in particular 2-3 equivalents of CCbBr or CCI4 for one equivalent cyclopentadiene.

Reaction step b):

Preferred bases for reaction step b) are alkali metal alcoholates, for example sodium tert-

10    butoxide and potassium tert-butoxide or metal amides like NaNH2 or lithiumdiisopropylamide. Except for ketones and esters, all inert solvents can be used. Appropriate solvents for reaction step b) are selected from methyl-tert-butylether (MTBE), methylcyclohexane (MCH) or a mixture thereof, tetrahydrofurane (THF), dyglime and toluene.

1S    A further appropriate solvent for reaction step b) is chlorobenzene.

Reaction step b) is advantageously performed at a temperature range of -20 to +20°C, preferably at temperatures of from -10 octo 10 °C, most preferably of from -soc to soc.

20    In a preferred embodiment of the present invention the compound of formula Ill (its solution) is used without isolation directly for the next reaction step. The compound of formula Ill is a valuable intermediate for the preparation of the compound of formula I. The compound of formula Ill is known from (a) Moberg, C.; Nilsson, M. J. Organomet. Chem. 1973, 49, 243-

248. (b) Siemionko, R. K.; Berson, J. A. J. Am. Chem. Soc. 1980, 102, 3870-3882.

2S However, the preparation method described in said reference is very unfavourable since: 1) The method could not be reproduced as described (low yield was obtained). 2) Utilizes very expensive pyrophoric and toxic starting material (nickelocene). 3) Produces large amount of metal-waste (nickel containing compounds). 4) The method cannot be scaled up

for industrial use (unavailability of nickelocen in large amounts, dangerous handling of large

30    quantities of nickelocen).

In contrast thereto, the preparation of the compound of formula Ill starting from cyclopentadiene is a novel and very efficient method and therefore constitutes a further object of the present invention.
 
Therefore, a further object of the present invention is a process for the preparation of the

compound of formula Ill
ClbCl
(Ill),


5    which process comprises

a) reacting cyclopentadiene in the presence of a radical initiator and CXCI3, wherein X is chloro or bromo, preferably bromo, to a compound of formula II
CCI30-x
(II),

wherein X is chloro or bromo,

10    and b) reacting the compound of formula II with a base in the presence of an appropriate solvent.

Reaction step c)

1,2-dehydro-6-nitrobenzene is generated in situ [for example, starting from a 6-15 nitroanthranilic acid of formula (A),
&NO, COOH
(A),

::::;,....
NH2

as described by L.Paquette et al, J. Amer. Chern. Soc. 99, 3734 (1977) and H. Seidel, Chemische Berichte, 34, 4351 (1901).

20    Reaction step c) is performed at elevated temperatures, preferably at temperatures of from 30°C to 60°C, most preferably of from 30 to 40°C.

Reaction step d)

Preferred metal catalysts for the hydrogenation reaction are selected from the group

25    consisting of Raney nickel, platinum, preferably platinum on a carrier like carbon, palladium, preferably palladium on a carrier like carbon but are not limited to said group. An especially
 

preferred catalyst is Raney nickel. Suitable hydrogen sources are hydrogen or hydrazine, preferably hydrogen.

Reaction step d) is performed at low to elevated temperatures, preferably at temperatures of from 0 to 80 •c. preferably of from 30 to 60 •c.

5

A preferred variant of the process according to the invention, comprises

aa) reacting cyclopentadiene with CXCh, wherein X is chloro, in the presence of a metal catalyst wherein the metal component of the catalyst is selected from ruthenium, copper, iron, palladium and rhodium, to a compound of formula II
CCI3

10    O-x<">•
wherein X is chloro,

b) reacting the compound of formula II with a base selected from alkali metal alcoholates in the presence of an appropriate solvent to the compound of formula Ill
Cl6Cl
(Ill),


15    c) and converting the compound of formula Ill in the presence of 1,2-dehydro-6-nitrobenzene to the compound of formula IV



(IV),


and

d) hydrogenating the compound of formula IV with a hydrogen source in the presence of a 20 metal catalyst.
 

Preparatory examples:

Example P1: Preparation of the compound of formula lla:

CCI
3•~.
v--sr (lla)

Azobisisobutyronitrile (2.5 g) was dissolved in bromotrichloromethane (250g).

5    Bromotrichloromethane (650 g) was loaded into a glass reactor under inert atmosphere

(nitrogen) and heated to 85 oc. 1/3 of the azobisisobutyronitrile solution (84 g) was added into the reactor at once and the reactor content was heated again to 85 oc followed by

simultaneous addition of the remaining 2/3 of azobisisobutyronitrile solution (168.5 g) and a

mixture of cyclopentadiene (100 g, freshly distilled) and methylcyclohexane (10 g) during 2.5

10    hours at 85°C. The reaction mixture was stirred for an additional1 hour at 85 oc, and then cooled to ambient temperature. Large amount of solvent (bromotrichloromethane) was evaporated in vacuum (60--+70°C, 150--+50 mbar). Methylcyclohexane (50 g) was added to

the distillation residue and the distillation was continued (60->70°C, 150--+15 mbar). The

crude product (distillation residue) was dried in vacuum for an additional 3D min (70°C, 15

15    mbar). Yield 389 g of the compound of formula lla in form of a brown oil, 94% pure, 92% yield, mixture of regioisomers.

Example P2: Preparation of the compound of formula Ill:
ClbCl
(Ill) .


20    A glass reactor was loaded with bromo(trichloromethyl)cyclopentene (27.83 g, compound

lla), methylcyclohexane (62 ml), methyl-tert-butylether (62 ml) and bis(2-methoxyethyl) ether (diglyme, 6.7 g) under inert atmosphere (nitrogen). The mixture was cooled to -10 oc in an ice/NaCI bath. Sodium tert-butoxide (20.3 g) was added into the reactor as solid during
10 min while keeping the temperature below +5 oc. When the addition was done, the

25    reaction mixture was stirred at 0-5 oc for 2 hours. The reaction mixture was quenched with a mixture of ice-cold water (80 ml) and ice (40 g) and then the pH value of the water phase was adjusted to =2 with 32% HCI (ca. 3 ml). The water phase was separated and the organic phase was dried over anhydrous potassium carbonate at 0°C. The potassium
carbonate was filtered off and rinsed with methyl-tert-butylether (10 ml). Methyl ethyl ketone (10 g) was added to the combined filtrate as internal standard and the concentration of 6,6-dichlorofulvene (compound of formula Ill) was determined by 1H NMR spectroscopy. Yield 81% [9.7 g of 9.9% (ca. 0.53 M) solution]. The solution was stored in a freezer and then
5    used for the next step.


Example P3: Preparation of the compound of formula IV:

Cl    Cl
;b (IV).
N02

10    A cold solution of 6,6-dichlorofulvene obtained in the previous step (9% in methyl-tert-butylether/methylcyclohexane = 1 :1) was placed in a glass reactor and heated quickly to 35"C. tert-pentyl nitrite (2.66 g) was added into the reactor followed by simultaneous addition

of tert-pentyl nitrite (9.46 g) and a solution of 6-nitroanthranilic acid (11.6 g, 96.6%) in methyl

ethyl ketone ( 42 ml) during 80 minutes at a temperature of 35"C. The reaction mixture was

15    stirred for additional 30 min at the same temperature and then all the volatiles were removed by rotary evaporation. The remaining residue was crystallized from methanol (20 ml) at +5"C for 15 hours. The brown crystalline material was filtered, washed with cold methanol (15 ml) and dried in air. Yield 7.10 g (42%, 98% pure product).

20    Example P4: Hydrogenation of the compound of formula IV:

An autoclave was charged with THF (130 ml), wet Raney-Nickel (2 g) and compound of formula IV (20 g). The autoclave was closed, the content started to agitate, purged three

times with nitrogen to remove oxygen and then three times with hydrogen. The reactor was

pressurized with hydrogen to 5 bar. Then the content of the autoclave was heated to 40 "C,

25    maintaining pressure with additional hydrogen as needed. When hydrogen uptake stopped, typically after 3 -4 h, the reaction mass was held another 30 min at 40 "C. After this time, the pressure was released and the content was cooled to ambient temperature. The solvent was removed under vacuum and the resulting oil crystallized upon standing to yield 18 g of the

yellowish to brownish compound  of formula I (96 %, 94% pure product).
 

30

Example P5: Preparation of CTCM-cyclopentene of formula lla using Grubbs-! cata~

CCI3•~  (lla)
\J---c1

A mixture of cyclopentadiene (2.0 g), azobisisobutyronitrile (0.5 g), benzylidene-bis(tricyclohexylphosphine)dichlororuthenium (Grubbs'151 Generation Catalyst, 12.2 mg,
5    0.05 mol%) and carbon tetrachloride (14 g) was heated at 75 oc under inert atmosphere (argon). The conversion was monitored by GC. After 4 hours the reaction was completed to produce chloro(trichloromethyl}cyclopentene as a mixture of three isomers in 85% yield (GC, dodecane was used as a standard).

10    Example P6: Preparation of CTCM-cyclopentene of formula lla using CuCifTMEDA catalyst.

CCI3•~  (lla)
\J---c1


Catalyst solution :

A mixture of copper (I} chloride (0.99 g), tetramethylethylenediamine (TMEDA, 2.32 g) and

15    acetonitrile (1 00 ml) was heated at 75 oc for 25 min under nitrogen atmosphere and then cooled to room temperature.
Cyclopentadiene solution:

Freshly prepared cyclopentadiene (66.0 g) was dissolved in carbon tetrachloride (307 g).

Reaction:

20    Under nitrogen atmosphere acetonitrile (80 g) and 40% of the catalyst solution were placed into a glass reactor under nitrogen. The mixture was heated to a temperature of 75 oc. Then 40% of the cyclopentadiene solution was added into the reactor in one portion followed by simultaneous addition of the rests of the catalyst solution and the cyclopentadiene solution

while keeping the temperature between 60 and 70 °C. The cyclopentadiene solution was

25    added in 1 hour and the catalyst solution in 1.5 hours. The reaction mixture was stirred for an additional 1 hour at 70 oc, cooled to ambient temperature and filtered. The solvent was removed by rotary evaporation and the residue was fractionated by vacuum distillation (40-45 °C, 0.1 mbar). Yield 170 g (75%, 97-98% purity), mixture of three regioisomers.
 

Example P7:  Preparation of the compound of formula Ill:

Cl    Cl
b {Ill) .

Sodium tert-butoxide (69.2 g) was stirred with chlorobenzene (175 ml) for 30 min at room

5    temperature to produce a fine suspension.

A glass reactor was loaded with chloro(trichloromethyl)cyclopentene (69.1 g), chlorobenzene (275 ml), and bis(2-methoxyethyl) ether (diglyme, 21.1 g) under inert atmosphere (nitrogen). The mixture was cooled to -20 "C and the suspension of sodium tert-butoxide was added

into the reactor portion-wise over 35 min while keeping the temperature below +3 "C. When

10    the addition was done, the reaction mixture was stirred at -5 "C for 3 hours.  The reaction

mixture was quenched with a mixture of 0.5 M aqueous HCI solution (300 ml) and ice (200 g). The pH value of the water phase was controlled to be pH =2. The water phase was separated and the organic phase was extracted with the same mixture of water and ice two

times {This was necessary for a complete removal of tert-butanol and diglyme). The

15    concentration of 6,6-dichlorofulvene was determined by 1H NMR spectroscopy using chlorobenzene (solvent) as an internal standard. Yield 75% [510 g of 6.8% (ca. 0.52 M) solution]. The solution was stored in a freezer or dry ice and then used for the next step. Comment: The yield just after the quench (no further extractions) was 85%. The solution was

lost in the phase separations.

20

A preferred benzonorbornene fungicide which can be advantageously prepared using the process according to the invention is 3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid (9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide of fonmula
v
~
~    Cl
",M""    (V).


N-N
\
CH 3

The compound of formula Vis described, for example, in WO 2007/048556. The compound of formula V can occur in two enantiomeric forms. The ccimpound of formula Va



    Cl   
ONH       
H    (Va),   
       
F       
M       
N-N       
\
CH3

5    which chemical designation is 3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid

( ( 1 S,4R)-9-dichloromethylene-1 ,2, 3,4-tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide, and the compound of formula Vb

R

O    NH

H    (Vb),   
       
F       
M       
N-N       
'CH3       

which chemical designation is 3-difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid

10    ( ( 1 R,4S)-9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-yl)-amide. The optical rotation angles [a]23•5 are -119.26° and +119.23° (in tetrahydrofurane) respectively.
 
What is claimed is:

1. A process for the preparation of 9-dichloromethylene-1 ,2,3,4-tetrahydro-1 ,4-methano-naphthalen-5-ylamine of formula I

5

which process comprises

a) reacting cyclopentadiene with CXCb. wherein X is chloro or bromo, in the presence of a radical initiator to a compound of formula II
CCI30-x(ll),

10    wherein X is chloro or bromo,

or aa) reacting cyclopentadiene with CXCI3 , wherein X is chloro, in the presence of a metal catalyst to a compound of formula II
CCI3
0-x,,l,

wherein X is chloro,

15    b) reacting the compound of formula II with a base in the presence of an appropriate solvent to the compound of formula Ill

Cl    Cl
I(  (Ill),
0

c) and converting the compound of formula Ill in the presence of 1,2-dehydro-6-nitrobenzene

to the compound of formula IV

(IV),


and

d) hydrogenating the compound of formula IV with a hydrogen source in the presence of a metal catalyst.
5

2. A process according to claim 1, which process comprises

a) reacting cyclopentadiene with CXCI3, wherein X is chloro or bromo, in the presence of a radical initiator to a compound of formula II
CCI30-x
(II).

10    wherein X is chloro or bromo. 3. The compound of formula IV
Cl    Cl
;b (IV).
N02

4. A process for the preparation of the compound of formula Ill
ClbCl    .
(Ill).

15

which process comprises

a) reacting cyclopentadiene with CXCh, wherein X is chloro or bromo, in the presence of a radical initiator to a compound of formula II
 


CCI3

0-x(ll),



wherein X is chloro or bromo,

and b) reacting the compound of formula II with a base in the presence of an appropriate

5    solvent.

5.    A process according to claim 4, wherein X is  bromo.

6.    A process according to claim 1, wherein aa) cyclopentadiene is reacted with CCI4 in the

10    presence of a metal catalyst to a compound of formula II

wherein X is chloro.

15    7. A process according to claim 1, which process comprises

aa)    reacting cyclopentadiene with CXCI3, wherein X is chloro, in the presence of a metal

catalyst wherein the metal component of the catalyst is selected from ruthenium, copper,

iron, palladium and rhodium, to a compound of formula II

CCI3
b-x<n>
20    wherein X is chloro,

b)    reacting the compound of formula II with a base selected from alkali metal alcoholates in

the presence of an appropriate solvent  to the compound of formula Ill
 
ClbCl
(Ill)
 


c)    and converting the compound of formula Ill in the presence of 1,2-dehydro-6-nitrobenzene to the compound of formula IV




(IV),


and

5    d) hydrogenating the compound of formula IV with a hydrogen source in the presence of a metal catalyst.

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