2,2-Dimethoxypropane → 3H,5H-Pyrrolo[1,2-c]oxazol-5-one, tetrahydro-3,3-dimethyl-, (R)-

温度

88 °C

To a mixture consisting of (R)-5-hydroxymethyl-2-pyrrolidinone (50.0 g, 434 mmol) in 2,2-dimethoxypropane (533 mL, 4300 mmol) was added camphorsulfonic acid (2.85 g, 10.8 mmol). The stirring mixture was brought to reflux at 88° C. for 1.5 hours, while removing methanol by distillation. The reaction mixture was subsequently heated to 95° C. for one hour, cooled to room temperature, treated with triethylamine (5 mL), and stirred for 5 minutes. The mixture was then diluted with hexanes-ethyl acetate (500 mL, 1:3 v/v) and washed sequentially with a 50% aqueous solution of sodium chloride and a saturated aqueous solution of sodium chloride. The organic phase was dried over sodium sulfate, filtered, and concentrated. The residue was purified by crystallization from hexanes to afford the title compound as white crystalline solid (30.48 g, 45%); TLC Rf 0.4 (solvent system: 5:95 v/v methanol:dichloromethane) MS (ESI+) m/z 156.1 (M+H)+, 178.1 (M+Na)+; 1H-NMR (CDCl3) δ 4.3-4.2 (m, 1H), 4.1 (dd, 1H), 3.5 (t, 1H), 2.9-2.7 (m, 1H), 2.6-2.5 (m, 1H), 2.2-2.1 (m, 1H), 1.9-1.7 (m, 1H), 1.7 (s, 3H), 1.5 (s, 3H).

1. customwhile removing methanol
2. distillationby distillation
3. temperatureThe reaction mixture was subsequently heated to 95° C. for one hour
4. temperaturecooled to room temperature
5. additiontreated with triethylamine (5 mL)
6. additionThe mixture was then diluted with hexanes-ethyl acetate (500 mL, 1:3 v/v)
7. washwashed sequentially with a 50% aqueous solution of sodium chloride
8. dry with materialThe organic phase was dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by crystallization from hexanes

ORDレコード

ord-301fcd800e7245cbacf878d370f978b2

出典データセット

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09440919B2