反应详情

温度

100 °C

A solution of boron trifluoride etherate (670 μL, 5.3 mmol) in dimethylformamide (2 mL) was cooled to −15° C. using an ice-acetonitrile bath, and then stirred for 15 min at this temperature. A solution of 6-methanesulfonyl-2-methyl-pyridin-3-ylamine (Intermediate 4; 653 mg, 3.5 mmol) in 1,2-dimethoxyethane (16 mL) was added dropwise to the solution at −15° C. and the stirring was continued for a further 15 min. tert-Butyl nitrite (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 90%; 483 mg, 4.2 mmol) was added dropwise, and the reaction mixture was stirred at −15° C. for 15 min and then at 0° C. for 1 h. Hexane (20 mL) was added and the solid was filtered off and washed with hexane. The solid was added to acetic anhydride (5 g, 49 mmol) and the mixture was heated at 100° C. for 1 h. The acetic anhydride was evaporated under high vacuum and then 1 M aqueous sodium carbonate solution was added. The mixture was extracted three times with dichloromethane. The dichloromethane was evaporated and the residue was purified by silica gel column chromatography, eluting with 0-40% ethyl acetate/hexane to give acetic acid 6-methanesulfonyl-2-methyl-pyridin-3-yl ester (331 mg, 41%) as a solid. 1H NMR (CDCl3) δ 2.39 (s, 3H), 2.52 (s, 3H), 3.22 (s, 3H), 7.62 (d, 1H, J=8.2 Hz), 7.98 (d, 1H, J=8.4 Hz).

1. waitthe stirring was continued for a further 15 min.
2. stirringthe reaction mixture was stirred at −15° C. for 15 min
3. waitat 0° C. for 1 h
4. filtrationthe solid was filtered off
5. washwashed with hexane
6. customThe acetic anhydride was evaporated under high vacuum
7. addition1 M aqueous sodium carbonate solution was added
8. extractionThe mixture was extracted three times with dichloromethane
9. customThe dichloromethane was evaporated
10. customthe residue was purified by silica gel column chromatography
11. washeluting with 0-40% ethyl acetate/hexane