反应详情

温度

80 °C

K2CO3 (3.15 g, 22.8 mmol) was added to a solution of 2-chloro-3-ethyl-4-fluorobenzonitrile (2.1 g, 11.4 mmol) and D-allo-threonine (2.04 g, 17.1 mmol) in DMSO (25 mL) at room temperature The reaction mixture was heated to 80° C. and stirred for 72 h then allowed to cool to room temperature. H2O (200 mL) was added and the brown solution was extracted with MTBE (200 mL). The aqueous layer was cooled to 0° C. and solid citric acid monohydrate was added in 200 mg portions until the evolution of as ceased. The aqueous layer was then extracted with EtOAc (3×200 mL). The combined organic layers were washed with brine (2×300 mL), dried with Na2SO4, filtered and concentrated to provide the title compound (1.44 g, 32%); 1H NMR (500 MHz, acetone-d6, δ in ppm) 7.47 (d, J=8.6 Hz, 2H), 6.70 (d, J=8.6 Hz, 2H), 5.46 (d, J=8.7 Hz, 1H), 4.55-4.43 (m, 1H), 4.27 (dd, J=5.9 Hz, 8.7 Hz, 1H), 2.90-2.81 (m, 2H), 1.33 (d, J=6.3 Hz, 3H), 1.21 (t, J=7.6 Hz, 3H).

1. temperatureto cool to room temperature
2. extractionthe brown solution was extracted with MTBE (200 mL)
3. temperatureThe aqueous layer was cooled to 0° C.
4. additionsolid citric acid monohydrate was added in 200 mg portions until the evolution of
5. extractionThe aqueous layer was then extracted with EtOAc (3×200 mL)
6. washThe combined organic layers were washed with brine (2×300 mL)
7. dry with materialdried with Na2SO4
8. filtrationfiltered
9. concentrationconcentrated