Hydrochloric Acid → HCID 178520920, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of methyl trans-4-(4-chlorophenyl)cyclohexanecarboxylate (compound of formula (VIIa)) (50.5 g, 200 mmol) in tetrahydrofuran (400 mL) at 0° C. under argon was added a 1M solution of lithium aluminium hydride in tetrahydrofuran (100 mL, 100 mmol) and the reaction mixture stirred for 30 minutes. The reaction mixture was cooled to 0° C. and 1M aqueous hydrochloric acid (500 mL, 500 mmol) was added and the mixture stirred for 5 minutes. The aqueous was separated and extracted with ethyl acetate (250 mL) then the combined organics were washed twice with water (2×125 mL). The resulting organics were concentrated under vacuum to a volume of 150 mL. The residue was diluted with ethyl acetate (250 mL) and the mixture concentrated under vacuum to a volume of 150 mL. The residue was diluted with ethyl acetate (250 mL) and the mixture concentrated under vacuum to a volume of 150 mL. The residue was diluted with ethyl acetate (250 mL) and the mixture concentrated under vacuum to a volume of 150 mL. To the resulting stirred mixture, at ambient temperature under argon, was added dimethyl sulfoxide (100 mL) and triethylamine (112 mL, 804 mmol). The mixture was cooled to 0° C. then pyridine sulphur trioxide complex (64 g, 402 mmol) was added in 4 equal portions and the reaction mixture stirred between 0 and 20° C. for 2 hours. Ethyl acetate (400 mL) was added, the mixture cooled to 0° C. with stirring and then 1M aqueous hydrochloric acid (400 mL, 400 mmol) was added. The resulting mixture was stirred at ambient temperature for 5 minutes then the organic layer was separated, diluted by the addition of ethyl acetate (500 mL) and washed with water (250 mL). The resulting organics were concentrated under vacuum to a volume of 200 mL, the residue diluted by the addition of ethyl acetate (500 mL) and then concentrated to a volume of 200 mL. The resulting mixture containing the title compound was used in the next step without analysis or purification.

Provenance & Evidence