Thionyl Chloride → 4-Piperidineacetic acid

Participants

Reaction Steps

A mixture of 2-(4-tert-butylphenyl)benzoic acid (0.02 mol) and thionyl chloride (0.04 mol) and DMF (5 drops) in DCM (50 ml) was stirred and refluxed for 1 hour. The solvent was evaporated and DCM (2×50 ml) was added and again the solvent was evaporated. The residue was dissolved in DCM (50 ml) and added to a solution of intermediate (18) (0.02 mol) and DIPEA (0.04 mol) in DCM (50 ml). The reaction mixture was stirred at room temperature for 4 hours. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 99.5/0.5). The product fractions were collected and the solvent was evaporated. The residue was dissolved in 2-propanol and DIPE and converted into the hydrochloric acid salt (1:1) with HCl/2-propanol. The residue was filtered off and dried, yielding 8.7 g of 4-piperidineacetic acid, 1-[4-[[[4′-(1,1-dimethylethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-α-phenyl-, methyl ester hydrochloride (1:1) 2-propanolate (1:1) (intermediate 19).

Provenance & Evidence