Potassium Carbonate → [5-(2,2,2-Trifluoro-1,1-dimethyl-ethyl)-isoxazol-3-yl]-carbamic acid phenyl ester

To a stirred mixture of 5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-amine prepared as described in Example 259A (2.34 g, 12.06 mmol) and potassium carbonate (5 g, 36 mmol) in dry dichloromethane (50 mL) at 0° C., was added a solution of phenyl chloroformate (2.83 g, 18 mmol) in anhydrous dichloromethane (5 mL). The reaction mixture was warmed to room temperature and stirred for a further 15 h, then additional phenyl chloroformate (1 g, 6.3 mmol) was added and stirring was continued for a further 3 h. The reaction mixture was partitioned between water (200 mL) and dichloromethane (500 mL). The organic layer was separated, washed with brine (100 mL), dried over MgSO4, and then concentrated under reduced pressure to give a yellow oil. Purification via silica gel flash chromatography (eluting with 5% to 50% ethyl acetate in hexanes) afforded phenyl 5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-ylcarbamate (2.63 g, 69%) as a colorless solid. 1H NMR (300 MHz, CDCl3) δ 8.16 (brs, 1H), 7.38-7.43 (m, 2H), 7.17-7.29 (m, 3H), 6.85 (s, 1H), 1.57 (s, 6H); LC-MS (ESI) m/z 315 (M+H)+.

1. customprepared
2. stirringstirring
3. waitwas continued for a further 3 h
4. customThe reaction mixture was partitioned between water (200 mL) and dichloromethane (500 mL)
5. customThe organic layer was separated
6. washwashed with brine (100 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated under reduced pressure
9. customto give a yellow oil
10. customPurification
11. washvia silica gel flash chromatography (eluting with 5% to 50% ethyl acetate in hexanes)

ORD-Eintrag

ord-b070bd2bd922489987475f159a603165

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09320739B2