ChemicalBook CAS DataBase List Rimonabant

Rimonabant synthesis

7synthesis methods

Product Name:Rimonabant
CAS Number:168273-06-1
Molecular formula:C22H21Cl3N4O
Molecular Weight:463.79

The reported preparation of rimonabant, both in small and large scale, is shown in the scheme. Lithium enolate formation of p-chlorophenyl ethyl ketone 54 with LiHMDS in THF at -78oC for 45 min followed by reaction with diethyl oxalate at -78oC and warming to room temperature over 16 h provided the lithium enolate salt of the diketoester 55. Reaction of diketoester salt 55 with 2,4-dichlorophenyl hydrazine (56) in ethanol at room temperature gave intermediate hydrazone 57 which is then cyclized in refluxing acetic acid for 24 h to obtain pyrazole ester 58. Hydrolysis of ester 58 with KOH in refluxing methanol:water mixture gave acid 59 which was then converted to the acid chloride 60 with thionyl chloride in refluxing toluene in very good yield. On scale, the synthesis of the acid chloride was performed in cyclohexane at 83oC. Reaction of acid chloride 60 with 1-aminopiperidine (61) in the presence of triethylamine at 0oC to room temperature over 3h gave rimonabant (VIII) which was isolated as the HCl salt by treating it with HCl in ether.

158681-13-1
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168273-06-1
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Yield:168273-06-1 93%

Reaction Conditions:

with methanol;potassium hydroxide;water at 0 - 5; for 1 h;

Steps:

1
EXAMPLE 1; Solid Phase III A solution of KOH (10,6 g) in methanol (87 mL) are added to a solution of Rimonabant hydrochloride (86.87 g) in methanol (347 mL). During the addition the internal temperature is maintained at 0-5°C. Once the addition is completed, water (174 mL) is added. The resulting suspension is cooled to 0-5°C and stirred during 1hs to the mentioned temperature. The solid is filtered and washed with water (3 x 300 mL). The solid is dried under vacuum at 50-55°C until to constant weight. In this trial, 74.50 g of crude solid is obtained (Yield: 93%)

References:

Vértessy, Miklós EP1944297, 2008, A1 Location in patent:Page/Page column 5-6

FullText

2213-43-6 Synthesis