反应详情

温度

-50 °C

To a stirred solution of LDA (3.1 eq) at −50° C. in THF was added methyl 3-chloro-2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-4-fluorobenzoate (Intermediate 47, 1.5 g, 4.96 mmol) in anhydrous THF (10 mL) dropwise and the solution was stirred for 1 h at −50° C. N-methoxy-N-methylacetamide (1.66 g, 14.9 mmol) in THF (5 mL) was added dropwise and stirring was continued for additional 1 h. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulphate. The solvent was removed under vacuum and the residue was purified over silica gel chromatography column using ethyl acetate-pet. ether gradient to obtain the title compound. Yield: 800 mg, (47%)

1. stirringstirring
2. waitwas continued for additional 1 h
3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride
4. extractionextracted with ethyl acetate
5. washThe organic layer was washed with brine
6. dry with materialdried over anhydrous sodium sulphate
7. customThe solvent was removed under vacuum
8. customthe residue was purified over silica gel chromatography column