反应详情

3-Bromopyridine (11.28 g, 0.0714 mol) in dry ether (50 ml) was added dropwise to a solution of n-butyl lithium (49.1 ml of a 1.6M solution in hexane, 0.0785 mol) in ether (150 ml) at -78° C. over 15 minutes. The resulting suspension was stirred for a further 15 minutes before N-methyl-N-methoxytrifluoroacetamide (D4, 11.22 g, 0.0715 mol) in ether (15 ml) was added dropwise. The reaction mixture was allowed to warm to room temperature over 1 h then poured into stirred ice-cold 2M hydrochloric acid (200 ml). The aqueous layer was separated and washed with ether (2×100 ml). The combined organic layers were extracted with 2M hydrochloric acid (150 ml). The combined aqueous layers were then carefully made basic then saturated with potassium carbonate and extracted with chloroform (4×250 ml). The combined chloroform extracts were dried (Na2SO4) and evaporated to give a semi-crystalline solid which was taken-up in toluene (300 ml) and treated with methoxylamine hydrochloride (18 g, 0.216 mol) at reflux under Dean-Stark conditions for 2 h. The reaction mixture was cooled and extracted with 2M hydrochloric acid (3×150 ml). The combined aqueous extracts were washed with ether (2×200 ml) then basified and partially saturated with potassium carbonate then extracted with chloroform (2×300 ml). The combined organic fractions were dried (Na2SO4) and evaporated to give an oil which was distilled to give the title compound (D7) as a colourless oil (11.64 g, 80%) b.p. 135° C. at 120 mmHg.

1. additionwas added dropwise
2. additionthen poured
3. customThe aqueous layer was separated
4. washwashed with ether (2×100 ml)
5. extractionThe combined organic layers were extracted with 2M hydrochloric acid (150 ml)
6. extractioncarefully made basic then saturated with potassium carbonate and extracted with chloroform (4×250 ml)
7. dry with materialThe combined chloroform extracts were dried (Na2SO4)
8. customevaporated
9. customto give a semi-crystalline solid which
10. temperatureat reflux under Dean-Stark conditions for 2 h
11. temperatureThe reaction mixture was cooled
12. extractionextracted with 2M hydrochloric acid (3×150 ml)
13. washThe combined aqueous extracts were washed with ether (2×200 ml)
14. extractionthen extracted with chloroform (2×300 ml)
15. dry with materialThe combined organic fractions were dried (Na2SO4)
16. customevaporated
17. customto give an oil which
18. distillationwas distilled