反应详情

To a suspension of sodium hydride (1.88 g as 60% in oil, 47.0 mmoles) which was washed with hexane to remove mineral oil and dried, in dimethylformamide (DMF, 23 ml) was added dropwise a solution of diethyl malonate (7.52 g, 47.0 mmoles) in DMF (5 ml) at 0° C. under the stream of nitrogen gas. After elevating the temperature to 50° C., a solution of 1-chloro-3-(2-fluoro-4-biphenylyl)butan-2-one (10.0 g, 36.1 mmoles) in DMF (40 ml) was added dropwise, and the resulting mixture was stirred at the same temperature for 2 hours. The reaction mixture was poured into ice water and extracted with diethyl ether. The organic layer was washed with 1M hydrochloric acid, dried over sodium sulfate and concentrated under reduced pressure. Purification of the residue by medium pressure silica gel column chromatography gave the desired diethyl 2-(3-(2-fluoro-4-biphenylyl)-2-oxobutyl)malonate (8.98 g, 22.4 mmoles, yield 62%) as a light yellow oil.

1. washwas washed with hexane
2. customto remove mineral oil
3. dry with materialdried, in dimethylformamide (DMF, 23 ml)
4. customto 50° C.
5. extractionextracted with diethyl ether
6. washThe organic layer was washed with 1M hydrochloric acid
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customPurification of the residue by medium pressure silica gel column chromatography