Diethyl Ether → 5-Fluoro-2-methylpyridine 1-oxide

温度

20 °C

Preparation 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).

1. additiontreated dropwise over 45 mins
2. temperatureThe solution was maintained at this temp
3. filtrationthe solid filtered off
4. customquickly transferred to a flask
5. customcovered with hexane (precooled to −20° C.)
6. waitstanding for 3 days
7. customthe hexane was decanted
8. addition2M NaOH solution added until basic (pH10)
9. filtrationThe mixture was filtered
10. extractionthe filtrate extracted with dichloromethane (10×200 ml)
11. customThe organic solution was dried
12. customevaporated to 200 ml
13. additiontreated with m-chloroperbenzoic acid (26.5 g)
14. washwas washed with excess aqueous sodium bicarbonate
15. extractionthe aqueous re-extracted with dichloromethane (10×200 ml)
16. customThe organic fraction was dried
17. customevaporated
18. customthe residue chromatographed (15% EtOH/EtOAc)

ORDレコード

ord-5d00d9c2d8cf43169e209aee62c92684

出典データセット

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07205408B2