Dichloromethane → (S)-N-benzyl-2-(4-hydroxy-2-oxopyrrolidin-1-yl)-4-methylthiazole-5-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of (4S)-4-(2-oxotetrahydro-2H-pyran-4-yloxy)pyrrolidin-2-one (0.036 g, 0.19 mmol), N-benzyl-2-bromo-4-methylthiazole-5-carboxamide (0.050 g, 0.16 mmol), cesium carbonate (0.079 g, 0.24 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (0.003 g, 0.003 mmol) and xantphos (0.004 g, 0.006 mmol) in anhydrous toluene (3 mL) was subjected to microwave irradiation at 80° C. for 20 min. The reaction mixture was diluted with ethyl acetate (10 mL) and washed with water (4 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in ethanol and a catalytic amount of pyridinium p-toluenesulfonate was added to the solution. The reaction mixture was heated at 50° C. for 6 hours and concentrated in vacuo. The residue was dissolved in dichloromethane (15 mL) and washed with water (5 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The obtained white solid was washed with diethyl ether (25 mL) and dried in air to afford the title compound (0.028 g, 53%): mp 203-204° C. (diethyl ether); 1H NMR (300 MHz, DMSO-d6) δ 8.60 (t, J=6.0 Hz, 1H), 7.33-7.17 (m, 5H), 5.46 (d, J=3.8 Hz, 1H), 4.47-4.41 (m, 1H), 4.35 (d, J=6.0 Hz, 2H), 4.12-4.04 (m, 1H), 3.93-3.85 (m, 1H), 3.00-2.90 (m, 1H), 2.48 (s, 3H), 2.42-2.33 (m, 1H); 13C NMR (75 MHz, DMSO-d6) δ 173.3, 162.1, 155.9, 140.0, 128.7, 127.7, 127.2, 119.4, 63.6, 57.0, 43.1, 41.7, 17.5; MS (ES+) m/z 332.2 (M+1).

Provenance & Evidence