反应详情

A mixture of 6-bromo-4-methyl-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Example #53, Step E, 2.0 g, 4.05 mmol), tert-butyl 3-amino azetidine-1-carboxylate (0.904 g, 4.85 mmol), diacetoxypalladium (0.091 g, 0.405 mmol), Cs2CO3 (2.64 g, 8.10 mmol) and BINAP (0.252 g, 0.405 mmol) in toluene (10 mL) was heated at reflux for 10 h. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether) to give 3-methyl-3-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester (2.2 g, 91%) as a pale yellow solid. 1H NMR (CDCl3, 400 MHz): δ 7.16 (s, 1H), 5.96 (brs, 1H), 5.13 (q, J=9.2 Hz, 2H), 4.61 (m, 1H), 4.56 (q, J=13.2 Hz, 2H), 4.41 (brs, 1H), 4.04 (m, 2H), 3.95 (d, J=12.4 Hz, 2H), 3.68 (m, 2H), 1.66 (s, 3H), 1.47 (d, J=6.4 Hz, 3H), 1.46 (s, 9H), 0.99 (m, 2H), 0.02 (s, 9H).

1. temperaturewas heated
2. temperatureat reflux for 10 h
3. filtrationfiltered
4. concentrationThe filtrate was concentrated in vacuo
5. customthe residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether)