Methanesulfonic Acid → 3-Methyl-1,4-oxazepan-5-one

Participants

Reaction Conditions

Reaction Steps

Methanesulfonic acid (20 mL) was added to a solution of 3-methyltetrahydro-4H-pyran-4-one (4-1, prepared by the method of Smith, A. B. et al. J. Am. Chem. Soc. 1991, 113, 2071, 3.00 g, 26.3 mmol, 1 equiv) in DME (30 mL) at −40° C. Sodium azide (5.13 g, 79.0 mmol, 3.00 equiv) was added in four equal portions over 30 min as cooling was maintained. The cold bath was then removed and the reaction mixture was warmed to 23° C. and stirred for 20 h. The mixture was diluted with DME (20 mL) and basified to pH 9 with concentrated aqueous ammonium hydroxide solution. The resulting mixture was partitioned between brine (200 mL) and a solution of 10% n-propanol in ethyl actetate (2×400 mL). The combined organic layers were dried over sodium sulfate and concentrated to give 3-methyl-1,4-oxazepan-5-one (4-2) as a pasty white solid. 1H NMR (300 MHz, CDCl3) δ 5.73 (br s, 1H), 3.97 (ddd, 1H,J=12.4, 5.6, 2.8 Hz), 3.83 (d, 1H,J=12.2 Hz), 3.76 (m, 1H), 3.66 (dd, 1H,J=12.4, 10.8 Hz), 3.35 (dd, 1H, J=12.2, 8.2 Hz), 2.89 (ddd, 1H,J=15.8, 10.8, 2.8 Hz), 2.54 (dd, 1H,J=15.8, 5.6 Hz), 1.15 (d, 3H,J=7.1 Hz).

Provenance & Evidence