Ammonium Chloride → tert-butyl 4-{2-[methoxy(methyl)amino]-2-oxo-1-(tetrahydro-2H-pyran-4-ylmethyl)ethyl}benzoate

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Reaction Steps

Lithium diisopropylamide (2M tetrahydrofuran solution, 6.9 mL) was diluted with tetrahydrofuran (20 mL), a solution of tert-butyl 4-{2-[methoxy(methyl)amino]-2-oxoethyl}benzoate (3.70 g) in a mixed solvent of tetrahydrofuran (20 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (12 mL) were added at −78° C., and the mixture was stirred for 1 hr. To the reaction mixture was added a solution of 4-(iodomethyl)tetrahydro-2H-pyran (3.30 g) in tetrahydrofuran m (20 mL) at −78° C. and the mixture was stirred for 3 hr. The mixture was slowly warmed to room temperature, and stirred overnight. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (3.81 g, yield 76%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio). MS: 378 (MH+).

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