Acetoacetic Acid → N-{(2S)-2-(4-fluorophenyl)-4-[3-(4-hydroxypiperidin-1-yl)azetidin-1-yl]butyl}-N-methyl-3,5-bis(trifluoromethyl)benzamide

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Reaction Steps

N-[(2S)-2-(4-Fluorophenyl)-4-oxobutyl]-N-methyl-3,5-bis(trifluoromethyl)benzamide (see Method 20; 0.40 g, 0.91 mmol) was dissolved in CH2Cl2 (10 mL) and to the resultant solution were added 1-azetidin-3-ylpiperidin-4-ol diacetate (see Method 15 with the exception that the diacetate was used rather than the corresponding dihydrochlorid; 0.28 g, 1.0 mmol) and DIPEA (0.76 g, 5.8 mmol). The mixture was stirred for a few minutes at RT and then sodium triacetoxyborohydride (0.43 g, 2.0 mmol) was added. The solution was stirred at RT overnight and then the solvent was removed by evaporation. The residue was partitioned between ethyl acetate and saturated NaHCO3 (aq). The phases were separated and the aqueous solution was extracted twice with ethyl acetate. The combined organic solutions were washed with water, dried over Na2SO4 and then the solvent was removed by evaporation. The residue was purified by flash chromatography using a mixture of methanol and CH2Cl2 as eluent. The product was dissolved in a mixture of water and acetonitrile and the solution was then freeze-dried. There was obtained 0.32 g (60%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): 1.4-3.8 (cm, 24H), 6.8-7.5 (cm, 6H), 7.9 (s, 1H); LCMS: m/z 576 (M+1)+.

Provenance & Evidence