Acetic Acid → α-(3-Chlorophenyl)-5,5-dimethyl-2-pyrrolidinemethanol

Participants

Reaction Conditions

Reaction Steps

35.4 ml (0.24 mols) of diisopropylamine are dissolved in 350 ml of tetrahydrofuran and cooled to −75° C. under nitrogen with a bath of dry ice and acetone. At this temperature, 180 ml (0.29 mols) of an approximately 1.6 molar solution of butyl lithium in hexane are added dropwise. By removing the cooling bath, the temperature is allowed to rise to −10° C. The solution of lithium-diisopropylamine thus obtained is again cooled to −78° C. This solution is mixed over the course of 20 minutes with 32 g (0.25 mols) of 1-nitroso-2,2-dimethylpyrrolidine and stirred for a further 10 minutes. Then, 35.2 g (0.25 mols) of 3-chlorobenzaldehyde are added dropwise over the course of 15 minutes, and the mixture is stirred for a further 3 hours at −75° C. To the resulting orange-coloured solution is then added dropwise, over the course of 20 minutes, a solution of 40 ml (0.7 mols) of glacial acetic acid in 80 ml of tetrahydrofuran. The reaction mixture which is now light yellow is warmed to room temperature by removing the cooling bath, and is then poured onto a mixture of 1 liter each of saturated sodium chloride solution and methyl chloride. After shaking out, the aqueous phase is separated and washed twice, each time with 200 ml of methylene chloride. The combined organic phases are washed with 200 ml of water, dried over sodium sulphate and the solvent residues are removed in a vacuum. The crystalline residue is dissolved whilst hot in a mixture of 180 ml of toluene and 270 ml of hexane. Upon cooling, the title substance is obtained in the form of white crystals having a m.p. of 143-144° C.

Provenance & Evidence