反应详情

Under nitrogen, 299 mL (4.20 mol) of acetyl chloride was added dropwise to a solution of 299 mL (5.11 mol) of absolute ethanol and 400 mL of chloroform at 0° C. A solution of 72.0 g (370 mmol) of 2-bromo-5-cyanomethylpyridine from step 5 in 1100 mL of chloroform was added dropwise with stirring. Stirring was continued at 0° C. for 4 h and the reaction was allowed to come to ambient temperature overnight. The reaction was diluted with 2500 mL of anhydrous ether and stirring was continued for an additional 2 h. The precipitated imidate hydrochloride salt was collected by filtration in a glove bag under nitrogen and washed with anhydrous ether. Under nitrogen, a mechanically stirred suspension of this material in 3500 mL of anhydrous ether at -78° C. was treated with 36 g (2.1 mol) of anhydrous ammonia. The reaction was allowed to slowly warm to ambient temperature overnight and the ammonium chloride removed by filtration. The filtrate was concentrated in vacuo giving 78.7 g (89%) of crude ethyl imino(2-bromopyridin-5-yl)acetate as a brown oil: NMR (CDCl3)δ1.29 (t, J=7 Hz, 3 H), 3.51 (s, 2 H), 4.13 (q, J=7 Hz, 2 H), 7.43 (dd, J=8 and 2 Hz, 1 H), 7.48 (d, J=8 Hz, 1 H), 8.26 (d, J=2 Hz, 1 H); MS (FAB) m/e (rel intensity) 245 (100), 243 (90), 217 (35), 215 (38), 200 (5), 198 (5).

1. stirringStirring
2. waitto come to ambient temperature overnight
3. stirringstirring
4. waitwas continued for an additional 2 h
5. filtrationThe precipitated imidate hydrochloride salt was collected by filtration in a glove bag under nitrogen
6. washwashed with anhydrous ether
7. additionUnder nitrogen, a mechanically stirred suspension of this material in 3500 mL of anhydrous ether at -78° C.
8. customthe ammonium chloride removed by filtration
9. concentrationThe filtrate was concentrated in vacuo