CS277268B6 - Process for preparing 1-bromocyclopentyl- (2-chlorophenyl) ketone - Google Patents

Abstract

1-Bromocyclopentyl-/2-chlorophenyl/-ketone is an intermediate for the production of 2- /2-chlorophenyl/-2-methylaminocyclohexanone hydrochloride. This substance is used in pharmacy under the generic name Ketamine in the form of injections as a short-acting narcotic. 1-Bromocyclopentyl-/2-chlorophenyl/-ketone is prepared by bromination of cyclopentyl-/2-chlorophenyl/-ketone without additional solvent. Hydrogen bromide is then removed from the product by vacuum distillation at 50 “C.

Description

1-Bromocyclopentyl- (2-chlorophenyl) -ketone of structural formula I \\

is an intermediate in the preparation of 2- (2-chlorophenyl) -2-methylaminocyclohexanone hydrochloride. This substance is used under the generic name Ketamine in pharmacy in the form of injections, as a short-acting narcotic.

1-Bromocyclopentyl (2-chlorophenyl) ketone is prepared by bromination of cyclopentyl (2-chlorophenyl) ketone with bromine in carbon tetrachloride. / DAS 1,293,761 /. This method has the disadvantage, on an operational scale, of working in a solvent which is a chemical carcinogen. Another disadvantage of the process is that the evaporation of carbon tetrachloride takes a long time after the bromination and that the remainder of this solvent always remains in the accumulated substance, which is disadvantageous for the further process. Hydrogen bromide, which is a by-product of bromination, is retained in the residual solvent. The high acidity of the substance produced then makes processing more difficult in the next production step.

The disadvantage of the process described is eliminated by the process according to the invention, which consists in brominating the cyclopentyl (2-chlorophenyl) ketone with bromine without solvent. There is no need for a solvent, as both reagents are liquids. After the bromination has ended, the hydrogen bromide residues are vacuum-distilled off after raising the temperature of the reaction mixture to 50 [deg.] C. Thus, the preparation is complete and the produced substance 1-bromocyclopentyl- (2-chlorophenyl) -ketone in a yield of practically 100% is suitable for further processing.

The advantage and progress of the process according to the invention is, on the one hand, the removal of the carcinogenic substance carbon tetrachloride from the production process, the shortening of the working time of the process and thus the increase in labor productivity. The removal of carbon tetrachloride from the production process also removes hydrogen bromide, which is always present in the solvent after bromination. The removal of hydrogen bromide from the product guarantees an increase in the yield of the final substance of the whole production process, i.e. 2- (2-chlorophenyl) -2-methylaminocyclohexanone hydrochloride by 10%.

Example

10.6 g of cyclopentyl (2-chlorophenyl) ketone are reacted directly without solvent with 8.7 g of bromine at a temperature of 20 to 25 ° C. After the reaction is complete, the contents of the reaction vessel are stirred for an additional 30 minutes. Hydrogen bromide is then vacuum distilled off under vacuum at 50 [deg.] C. for one hour. After cooling the reaction mixture to 5 DEG C., 14.6 g of 1-bromocyclopentyl- (2-chlorophenyl) ketone (100% of th) are obtained. The substance complies with the control by thin layer chromatography.

Claims (1)

PATENT CLAIMS Process for the preparation of 1-bromocyclopentyl (2-chlorophenyl) ketone by bromination of cyclopentyl (2-chlorophenyl) ketone with bromine, characterized in that the bromination is carried out without additional solvent, the hydrogen bromide then being removed from the product by vacuum distillation at 50 ° C. .