反应详情

Under argon, 44.2 g (85% purity, 216 mmol) of 3-bromopyridone in 450 ml of N-methylpyrrolidone were introduced as initial charge, and 29.1 g of potassium tert-butanolate (259 mmol) were added in portions such that the temperature remained below 30° C. The mixture was stirred for 1 h and then 40 g (216 mmol) of 1-fluoro-2-(methoxymethyl)-4-nitrobenzene were added. The reaction mixture was stirred for 4 h at 80° C., cooled to RT and stirred into an ice/water mixture. The pH was adjusted to pH=4 with semi-concentrated hydrochloric acid, the mixture was extracted with ethyl acetate, and the organic phase was dried over sodium sulphate, filtered and evaporated to dryness on a rotary evaporator. The residue was dissolved in 2 l of dichloromethane, absorbed on five times the amount of silica gel and chromatographically purified on silica gel with ethyl acetate:dichloromethane 3:97 and 5:95. The product fractions were evaporated to dryness on a rotary evaporator and the residue was dried in vacuo. This gave 55 g (73%) of the desired product.

1. additionas initial charge
2. customremained below 30° C
3. stirringThe reaction mixture was stirred for 4 h at 80° C.
4. extractionthe mixture was extracted with ethyl acetate
5. dry with materialthe organic phase was dried over sodium sulphate
6. filtrationfiltered
7. customevaporated to dryness on a rotary evaporator
8. dissolutionThe residue was dissolved in 2 l of dichloromethane
9. customabsorbed on five times the amount of silica gel
10. customchromatographically purified on silica gel with ethyl acetate:dichloromethane 3:97 and 5:95
11. customThe product fractions were evaporated to dryness on a rotary evaporator
12. customthe residue was dried in vacuo