反应详情

温度

75 °C

2-chloro-4-fluorobenzonitrile (60702-69-4) (2.0 g, 12.86 mmol) was mixed together with H-D-Thr-OH (1.84 g, 15.43 mmol) in DMSO (30 mL). K2CO3 (3.73 g, 27.0 mmol) was added to the reaction mixture and stirred at 75° C. for 24 h. The reaction mixture was cooled down to room temperature and poured slowly into a 10% citric acid solution and stirred for 10 min at room temperature. The solution was extracted with EtOAc several times to get the crude product. The crude product was chromatographed with a gradient of hexane EtOAc and then with EtOAc, 100% to get the pure final product 1.8 g): 1H NMR (500 MHz, acetone-d6, δ in ppm) 7.51 (d, J=9 Hz, 1H), 6.95 (s, 1H), 6.82 (d, J=9 Hz, 1H), 5.17 (d, J=9 Hz, 1H), 4.42 (m, 1H), 4.22 (d, J=6 Hz, 1H), 2.34 (s, 3H), 1.28 (d, J=6 Hz, 3H).

1. temperatureThe reaction mixture was cooled down to room temperature
2. stirringstirred for 10 min at room temperature
3. extractionThe solution was extracted with EtOAc several times
4. customto get the crude product
5. customThe crude product was chromatographed with a gradient of hexane EtOAc