Ammonium Chloride → 1-(Tetrahydro-2H-pyran-4-yl)ethanone

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Reaction Steps

Add 2 M isopropylmagnesium chloride in tetrahydrofuran (520.22 mL, 3.0 eq) to a mixture of methyl tetrahydro-2H-pyran-4-carboxylate (46.30 mL, 346.81 mmol) and N,O-dimethylhydroxylamine hydrochloride (52.44 g, 1.6 eq) in tetrahydrofuran (2.43 L) during 15 minutes at −20° C. under nitrogen. After 30 min, add saturated aqueous ammonium chloride (400 mL) to the reaction at −20° C. Extract the aqueous solution with methyl tert-butyl ether (250 mL×3). Wash the combined organics with saturated aqueous sodium chloride. Dry over anhydrous magnesium sulfate and concentrate in vacuo. Add dichloromethane (500 mL), filter through Celite® and concentrate in vacuo. Add tetrahydrofuran (700 mL), then add 3 M methyl magnesium chloride in tetrahydrofuran (231.21 mL, 2.0 eq) dropwise over 15 minutes at 7° C. After 40 minutes, add saturated aqueous ammonium chloride (250 mL) to the reaction. Extract the aqueous solution with methyl tert-butyl ether (250 mL×2). Dry over anhydrous magnesium sulfate and concentrate in vacuo. Purify by silica gel chromatography, eluting with 2:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate, to give 1-(tetrahydro-pyran-4-yl)-ethanone (33.18 g, 75%). 1H NMR (300 MHz, DMSO-d6) δ 3.98 (m, 2H), 3.42 (m, 2H), 2.52 (m, 1H), 2.15 (s, 3H), 1.74 (m, 4H).

Provenance & Evidence