Dimethyl Sulfoxide → HCID 20811361, compound

Participants

Reaction Conditions

Reaction Steps

In a round-bottomed flask fitted with a reflux condenser and a thermometer were introduced 3 g (6.13 mmoles) of (S)-2-{4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazin-1-yl}-acetamide dissolved in 30 ml of CH2Cl2 (compound 144 prepared at example 1.4.1 above). The solution was cooled to −78° C. and DMSO (0.7 ml, 9.8 mmoles) and oxalyl chloride (0.6 ml, 7.4 mmoles) were added. After 15 minutes, triethylamine (2.5 ml, 18.4 mmoles) was added dropwise and the reaction mixture was stirred at −70° C. until complete disappearance of the starting material. The reaction was quenched with water and the pH was adjusted to 11 by addition of aqueous NaOH. The aqueous solution was extracted with CH2Cl2 and the combined organic layers were dried over MgSO4 and concentrated. The crude was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/NH3: 98/2/0.2 v/v/v) to yield (S)-{4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazin-1-yl}-acetonitrile (compound 291, 2.14 g, 73%) as a pale yellow powder which was converted into the dichydrochloride salt by reaction with HCl in diethylether.

Provenance & Evidence