Tetrabutylammonium Fluoride → 3-(4(S)-methyl-3-oxo-7-trifluoromethyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a solution of 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 (1.6 g, 2.73 mmol) in THF (5 mL) was added a solution of TBAF (1 M in THF, 4.1 mL, 4.1 mmol). The reaction mixture was heated at reflux for 3 days then cooled to ambient temperature. The solvent was removed in vacuo and the residue was purified by chiral SFC separation (Table 2, Method 2) to give 3-(4(S)-methyl-3-oxo-7-trifluoromethyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (Enantiomer 1, SFC (Table 1, Method 6), Rt=8.78 min., 0.280 g, 22%) and 3-(4(R)-methyl-3-oxo-7-trifluoromethyl-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (Enantiomer 2, SFC (Table 1, Method 6), Rt=10.53 min., 0.260 g, 21%). 1H NMR (CDCl3, 400 MHz): δ 8.18 (s, 1H), 7.18 (s 1H), 5.91 (s, 1H), 4.68 (q, J=6.8 Hz, 1H), 4.61 (d, J=12.8 Hz, 1H), 4.52 (m, 1H), 4.51 (d, J=12.8 Hz, 1H), 4.36 (m, 2H), 4.22 (m, 1H), 3.80 (m, 2H), 1.55 (d, J=6.8 Hz, 3H), 1.49 (m, 9H).

Provenance & Evidence