反应详情

A 50-mL round-bottomed flask was charged with (S)-tert-butyl 1-(dimethylamino)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (6c) (860 mg, 2.0 mmol, 1.0 equiv) and 4N HCl in dioxane (5.0 mL). The reaction mixture was stirred at room temperature for 2 h, then concentrated under reduced pressure and maintained at ˜1 torr for 1 h. The resulting white, foamy solid was dissolved in CH2Cl2 (10 mL). Et3N (562 μL, 4.0 mmol, 2.0 equiv) and 3,5-bis(trifluoromethyl)phenylisothiocyanate (596 mg, 2.2 mmol, 1.1 equiv) were added sequentially via syringe. The flask was capped with a plastic stopper, and the reaction mixture was stirred at room temperature for 14 h. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to purification by flash column chromatography on silica gel (gradient elution, 3:1 hexanes/Et2O→1:1 hexanes/Et2O) to provide the product (4a) as a white solid (613 mg, 1.43 mmol, 71% yield over two steps). [α]D25=−32.8° (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ 9.06 (1H, s), 7.90 (2H, s), 7.77 (1H, d, J=9 Hz), 7.56 (1H, s), 5.68 (1H, d, J=9 Hz), 3.35 (3H, s), 2.97 (3H, s), 1.12 (9H, s). 13C {1H}NMR (100 MHz, CDCl3): δ 181.8, 174.0, 140.3, 131.7 (q, JC-F=33 Hz), 123.7 (m), 123.3 (q, JC-F=272 Hz), 118.1 (m), 60.9, 39.1, 36.2, 36.0, 27.2. IR (cm−1): 3322 (br m), 2972 (m), 1611 (m), 1532 (s), 1474 (m), 1385 (m), 1274 (s), 1174 (m), 1126 (s), 963 (m), 883 (m), 848 (w), 700 (m), 680 (m). LRMS (ESI): 452.1 (60%) [M+Na]+.

1. concentrationconcentrated under reduced pressure
2. temperaturemaintained at ˜1 torr for 1 h
3. dissolutionThe resulting white, foamy solid was dissolved in CH2Cl2 (10 mL)
4. customThe flask was capped with a plastic stopper
5. stirringthe reaction mixture was stirred at room temperature for 14 h
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. customthe residue was subjected to purification by flash column chromatography on silica gel (gradient elution, 3:1 hexanes/Et2O→1:1 hexanes/Et2O)