Diethyl Ether → 5-Fluoro-2-methylpyridine 1-oxide
反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:8])=[N:6][CH:7]=1.NC1C=CC(C)=NC=1.N(OCCCC)=[O:18].CCOCC>C(O)C.F[B-](F)(F)F.[H+]>[F:1][C:2]1[CH:7]=[N+:6]([O-:18])[C:5]([CH3:8])=[CH:4][CH:3]=1[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:8])=[N:6][CH:7]=1.NC1C=CC(C)=NC=1.N(OCCCC)=[O:18].CCOCC>C(O)C.F[B-](F)(F)F.[H+]>[F:1][C:2]1[CH:7]=[N+:6]([O-:18])[C:5]([CH3:8])=[CH:4][CH:3]=1Preparation of 5-fluoro-2-picoline was based on E. J. Blanz, F. A. French, J. R. DoAmaral and D. A. French, J. Med. Chem. 1970, 13, 1124–1130. 5-Amino-2-picoline (12.5 g) in ethanol (105 ml) and 50% fluoroboric acid (44.5 ml) was stirred at −5° C. and treated dropwise over 45 mins. with n-butyl nitrite (31.25 ml). The solution was maintained at this temp. for 3 hours, treated with ether (100 ml, precooled to −20° C.) and the solid filtered off, quickly transferred to a flask and covered with hexane (precooled to −20° C.). After allowing to warm to approx. 20° C. and standing for 3 days the hexane was decanted and 2M NaOH solution added until basic (pH10). The mixture was filtered and the filtrate extracted with dichloromethane (10×200 ml). The organic solution was dried, evaporated to 200 ml and treated with m-chloroperbenzoic acid (26.5 g). After stirring 16 hours the solution was washed with excess aqueous sodium bicarbonate and the aqueous re-extracted with dichloromethane (10×200 ml). The organic fraction was dried and evaporated and the residue chromatographed (15% EtOH/EtOAc) to give the product (5.5 g).
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