反应详情

A 1-L 3-neck rbf was fitted with an overhead stirrer and charged with sodium hydride (60% dispersion in mineral oil, 2.19 g, 54.6 mmol) and DMF (550 mL). Ethyl 4-{4-[(tert-butoxycarbonyl)amino]-3-fluorophenyl}-5-cyano-1H-pyrrole-3-carboxylate (10.00 g, 45.5 mmol) was added and the mixture was left to stir at rt for 15 min. The reaction mixture was treated with (aminooxy)(diphenyl) phosphine oxide (12.74 g, 54.6 mmol) and heated to 60° C. The very thick reaction mixture gradually became a readily stirred suspension. After 1 h analysis by RP-HPLC indicated that all starting material had been consumed. The reaction was cooled to rt and diluted with 1.5 L EtOAc and aq. sodium bicarbonate. The aqueous layer was back extracted with EtOAc (2×) and the combined organic layers were dried (sodium sulfate) and filtered through a silica plug. Trituration with ether:hexanes (1:2) gave the title compound as a yellowish powder (18.06 g, 46.5 mmol, 93.7%). 1H-NMR (DMSO-d6) δ 9.13 (s, 1H), 7.68 (s, 1H, 7.68 (t, J=8 Hz, 1H), 7.29 (dd, J=12, 2 Hz, 1H), 7.19 (dd, J=8 Hz, 1H), 6.67 (s, 2H), 4.14 (q, J=7 Hz, 2H), 1.50 (s, 9H), 1.18 (s, 3H); MS [M+Na]+=411.0; LCMS RT=3.48.

1. customA 1-L 3-neck rbf was fitted with an overhead stirrer
2. waitthe mixture was left
3. temperatureheated to 60° C
4. waitAfter 1 h analysis by RP-HPLC indicated that all starting material
5. customhad been consumed
6. temperatureThe reaction was cooled to rt
7. additiondiluted with 1.5 L EtOAc and aq. sodium bicarbonate
8. extractionThe aqueous layer was back extracted with EtOAc (2×)
9. dry with materialthe combined organic layers were dried (sodium sulfate)
10. filtrationfiltered through a silica plug