反应详情

温度

2.5 °C

To a solution of (R)-tert-butyl 3-((R)-(2-aminoethoxy)(3-chloro-5-fluorophenyl)methyl)piperidine-1-carboxylate (1.1 g, 2.85 mmol) in dry CH2Cl2 (20 mL), Et3N (2 mL) was added. The resulting mixture was cooled to 0-5° C. under ice-water bath, a solution of ethyl chloroformate (615 mg, 5.7 mmol) in dry CH2Cl2 (2 mL) was added dropwise. After addition, the reaction mixture was stirred for 1-2 hr at rt. Water (20 mL) was added to quench the reaction. The aqueous layer was extracted with CH2Cl2 (3×20 mL), the combined organic layers were dried over Na2SO4, filtered and concentrated to give the crude (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(2-(ethoxycarbonylamino)ethoxy)methyl)piperidine-1-carboxylate (1.3 mg, 100%). 1H NMR (CD3OD, 400 MHz) δ 7.01 (d, 2H), 6.87 (d, 1H), 4.32 (m, 2H), 4.09 (m, 2H), 3.92 (m, 2H), 3.33 (m, 5H), 1.75 (s, 1H), 1.55 (m, 1H), 1.43 (s, 9H), 1.34 (m, 2H), 1.23 (t, 3H), 1.09 (t, 1H).

1. additionAfter addition
2. customto quench
3. customthe reaction
4. extractionThe aqueous layer was extracted with CH2Cl2 (3×20 mL)
5. dry with materialthe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated