1,2-Dichloroethane → (S)-N-(3,4-Dimethyl-phenyl)-2-hydroxy-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamide

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Reaction Steps

To a solution of (3,4-dimethyl-phenyl)-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amine (800 mg, 0.27 mmol, prepared as described in example 1, step 3) in CH2Cl2 (3 mL) was added under a nitrogen atmosphere at 0° C. benzoylformic acid (61 mg, 0.41 mmol), EDC (130 mg, 0.68 mmol). After stirring for 1 h, the mixture was concentrated and redissolved in MeOH (3 mL) and treated with NaBH4 (206 mg, 5.44 mmol) and stirring continued for 3 h at ambient temperature. It was diluted with TBME (15 mL) and aqueous K2CO3 (2 M, 15 mL), stirred further for 20 min, the layers separated and the organic layer washed with water (15 mL). The combined aqueous layers were extracted with TBME (15 mL) and the combined organic layers dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 60:40) afforded the racemic compound (78 mg, 67%) as a pale yellow oil. MS m/e: 429.2 [M+H]+ which was then separated by chiral HPLC to provide the title compound as an off white solid MS m/e: 429.2 [M+H]+.

Provenance & Evidence