Methanol → HCID 86590286, compound

Participants

Reaction Conditions

Reaction Steps

In a round-bottomed flask fitted with a reflux condenser and a thermometer were introduced {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; 0.5 g, 0.8 mmoles), Et3N (0.26 ml, 1.8 mmoles), MeOH (3 ml) and DMF (9 ml). The mixture was purged with N2 and a stream of CO was passed into the mixture for 10 min. A solution of Pd(OAc)2 (19.2 mg, 10% moles) and Diphenylphosphinopropane (Dppp) (33 mg, 10% moles) dissolved in MeOH/DMF 1/3 (0.65 ml), purged with N2, was then added to the mixture. The reaction mixture was heated at 70° C. and CO was bubbled through the reaction mixture overnight. The reaction mixture was purged with N2, quenched with NaHCO3 and extracted with AcOEt. The combined organic layers were dried over MgSO4 and concentrated to give an oil which was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/NH3: 99.5/0.5/0.1 v/v/v) to afford 4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-(4-methoxycarbonylmethyl-piperazin-1-yl)-ethyl]-benzoic acid methyl ester (compound 316; 150 mg, 30%).

Provenance & Evidence