反应详情

温度

-50 °C

4.3 ml of a 1.3 M solution of sec-butyllithium in 98/2 v/v cyclohexane/hexane are added dropwise, while maintaining the temperature between −40° C. and −30° C., to a solution of 0.5 g of tert-butyl (3-fluoro-2-methylphenyl)carbamate in 10 ml of tetrahydrofuran under argon and cooled to −40° C. The reaction mixture is then cooled to −50° C., and then a solution of 0.27 ml of N-methoxy-N-methylacetamide in 4 ml of tetrahydrofuran is added dropwise while maintaining the temperature between −50° C. and −40° C. The mixture is then left to warm up to approximately −10° C., and then stirred at this temperature for 0.5 hour. It is then treated with 5.6 ml of a 1N hydrochloric acid solution and then diluted with 20 ml of diethyl ether and left to warm up to ambient temperature with stirring for 1 hour. After settling out, the organic phase is separated and the aqueous phase is extracted with 40 ml of diethyl ether. The organic phases are combined, washed with 3×40 ml of water, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 30 g cartridge of 15-40 μm silica, elution being carried out with a 90/10 v/v cyclohexane/ethyl acetate mixture, at a flow rate of 30 ml/min, and then on a 30 g cartridge of 15-40 μm silica, elution being carried out with pure dichloromethane, at a flow rate of 30 ml/min. 0.38 g of tert-butyl [3-fluoro-2-(2-oxopropyl)phenyl]carbamate is thus obtained, in the form of a white solid, the characteristics of which are the following:

1. temperaturewhile maintaining the temperature between −40° C. and −30° C.
2. temperaturewhile maintaining the temperature between −50° C. and −40° C
3. waitThe mixture is then left
4. temperatureto warm up to approximately −10° C.
5. waitleft
6. temperatureto warm up to ambient temperature
7. stirringwith stirring for 1 hour
8. customthe organic phase is separated
9. extractionthe aqueous phase is extracted with 40 ml of diethyl ether
10. washwashed with 3×40 ml of water
11. dry with materialdried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated to dryness under reduced pressure
14. customThe residue is purified by chromatography on a 30 g cartridge of 15-40 μm silica, elution
15. washon a 30 g cartridge of 15-40 μm silica, elution