Cesium carbonate → 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

Participants

Reaction Steps

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, 0.110 g, 0.223 mmol), tert-butyl 3-amino-3-methylazetidine-1-carboxylate (0.062 g, 0.334 mmol), Pd(OAc)2 (0.010 g, 0.045 mmol), cesium carbonate (0.109 g, 0.334 mmol) and BINAP (0.042 g, 0.067 mmol) in toluene (5 mL) was heated at reflux for 5 h. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (eluting with 20% 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 (0.090 g, 67%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 7.13 (s, 1H), 5.93 (s, 1H), 5.10 (q, J=10.4 Hz, 2H), 4.62 (d, J=12.8 Hz, 1H), 4.58 (m, 1H), 4.49 (d, J=12.8 Hz, 1H), 4.37 (s, 1H), 4.00 (m, 2H), 3.95 (m, 2H), 3.66 (t, J=8.0 Hz, 2H), 1.63 (s, 3H), 1.47 (d, J=6.8 Hz, 3H) 1.45 (s, 9H), 0.99 (m, 2H), 0.00 (s, 9H).

Provenance & Evidence