反应详情

温度

-78 °C

To a cold (−23° C.), stirred solution of tert-butyl 2-methoxyphenylcarbamate (443.3 mg, 1.986 mmol) in ether (5 mL) under N2 was added t-BuLi (2.6 mL, 4.42 mmol). The reaction mixture was stirred for 2 h, and then cooled to −78° C. To the reaction mixture was added a solution of methyl 5-(trifluoromethyl)picolinate (501.3 mg, 2.44 mmol) in ether (10 mL) dropwise via cannula over 5 min. After 2 h, the reaction mixture was warmed to room temperature, stirred for an additional hour, and then the reaction was quenched by the addition of water with vigorous stirring. The reaction mixture was diluted with EtOAc, the organic phase was separated, washed with sat NaCl then dried (Na2SO4), filtered and concentrated to yield a yellow solid. The residue was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 100% solvent A/B=hexane/EtOAc, REDISEP® SiO2 40 g) to obtained Intermediate A-28A (546.8 mg, 69.5% yield)) as a yellow solid: 1H NMR (400 MHz, chloroform-d) δ ppm 8.83-8.88 (1H, m), 8.24 (1H, d, J=8.4 Hz), 8.07 (1H, dd, J=8.4, 1.8 Hz), 7.25 (1H, d, J=1.5 Hz), 7.18-7.24 (1H, m), 7.09 (1H, dd, J=8.0, 1.7 Hz), 6.95 (1H, s), 3.93 (3H, s), 1.25 (9H, s).

1. waitAfter 2 h
2. temperaturethe reaction mixture was warmed to room temperature
3. stirringstirred for an additional hour
4. customthe reaction was quenched by the addition of water with vigorous stirring
5. additionThe reaction mixture was diluted with EtOAc
6. customthe organic phase was separated
7. washwashed with sat NaCl
8. dry with materialthen dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto yield a yellow solid
12. customThe residue was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 100% solvent A/B=hexane/EtOAc, REDISEP® SiO2 40 g)
13. customto obtained Intermediate A-28A (546.8 mg, 69.5% yield)) as a yellow solid