Dimethylformamide → (+)-4-Phenyl4-[(1-(3,5-bis(trifluoromethyl)phenyl)-2-hydroxyethoxy)methyl]-1-(2-(pyrrolidinyl)acetamido)piperidine Hydrochloride

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Reaction Steps

(1-Pyrrolidinyl)acetic acid (0.68 g) in dry dimethyl formamide (20 ml) was treated with triethylamine (1.38 ml) and cooled to -30° C. iButyl chloroformate (0.55 ml) was added and the reaction stirred for 10 minutes before adding the compound of Example 1 (1.0 g). The solution was allowed to warm slowly to room temperature then stirred for 16 hours. The solution was concentrated under reduced pressure then ethyl acetate was added and washed with aqueous sodium chloride, then dried and concentrated to give an oil which was dissolved in methanol and stirred with potassium carbonate for 1 hour. The solvent was evaporated and the residue partitioned between ethyl acetate and aqueous sodium chloride. The organic solution was dried (Na2SO4) and concentrated to give a residue which was purified by chromatography on neutral alumina eluting with 1% methanol/dichloromethane. The resulting product was treated with ethereal hydrogen chloride to give a white solid which was recrystallised from ethyl acetate to give the title compound; mp 110°-112° C.; MS (Cl+) 559 (M+H)+ ; 1H NMR (360 MHz, d6 -DMSO) δ 1.78-2.32 (8H, m), 2.96-3.18 (4H, m), 3.29 (1H, d, J=9.1 Hz), 3.38-3.60 (6H, m), 3.80-3.95 (1H, m), 4.24-4.33 (1 H, m), 4.38-4.47 (2H, m), 7.23 (1H. t, J=7.5 Hz), 7.34 (2H, t, J=7.5 Hz), 7.41 (2H, t, J=7.5 Hz), 7.68 (1H, s), 7.70 (1H, s) and 7.96 (1H, s).

Provenance & Evidence