N-methyl-2-pyrrolidone → HCID 86590288, compound

Participants

Reaction Conditions

Reaction Steps

A round-bottomed flask charged with Pd(OAc)2 (36 mg, 4% moles) and P(o-tol)3 (192 mg, 20% mol) was evacuated and then vented to nitrogen. N-methylpyrrolydone (NMP) (4 ml) was added and the mixture was heated at 50° C. for 30 min. Diethylzinc in hexane (0.29 ml) was added and the mixture was maintained at 50° C. for an additional 30 min. The mixture was cannulated into a flask containing a solution of {4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-(4-bromo-phenyl)-ethyl]-piperazin-1-yl}-acetic acid methyl ester (compound 184 prepared at example 1.4.1 above; 2.33 g, 4.0 mmoles) and Zn(CN)2 (0.47 g, 4.0 mmoles) dissolved in NMP (6 ml). The reaction mixture was heated at 60° C. for 3 hours. The eluent was evaporated and the residue was taken up in diethylether. The precipitate was filtered and the organic solution was washed with ammonium hydroxyde, dried over MgSO4 and concentrated. The residue was purified by chromatography on silica gel (eluent: Hex/AcOEt: 75/25 v/v) to give {4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-(4-cyano-phenyl)-ethyl]-piperazin-1-yl}-acetic acid methyl ester (compound 317; 0.9 g, 34%).

Provenance & Evidence