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

Temperature

23 °C

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).

1. customprepared by the method of Smith
2. customat −40° C
3. temperatureas cooling
4. temperaturewas maintained
5. customThe cold bath was then removed
6. additionThe mixture was diluted with DME (20 mL)
7. customThe resulting mixture was partitioned between brine (200 mL)
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. concentrationconcentrated

ORD record

ord-5855b1f2f3d548bc8d285e85afc6b36e

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623863B2