反应详情

温度

2.5 °C

A solution of (R)-tert-butyl 3-((R)-(2-aminoethoxy)(3-chloro-5-fluorophenyl)methyl)piperidine-1-carboxylate (24 g, 0.062 mol) in dry CH2Cl2 (300 mL) and Et3N (31.4 g, 43 mL) was cooled to 0° C. in ice-water bath, a solution of methyl chloroformate (11.8 g, 0.124 mol) in dry CH2Cl2 (100 mL) was added dropwise. After addition, the reaction mixture was stirred for 1-2 h at 0-5° C. Water (200 mL) was added to quench the reaction. The aqueous layer was extracted with CH2Cl2 (3×100 mL), the combined organic layers were washed with 10% citric acid (2×80 mL) and brine, then dried over Na2SO4, filtered and concentrated to give the crude product, which was purified by column chromatography to give (R)-tert-butyl 3-((R)-(3-chloro-5-fluorophenyl)(2-(methoxycarbonylamino)ethoxy)methyl)piperidine-1-carboxylate (19 g, 0.043 mol). 1H NMR (CD3OD) δ 7.17 (s, 1H), 7.16-7.08 (m, 1H), 7.07-7.00 (m, 1H), 4.20-4.00 (m, 2H), 3.90-3.78 (d, 1H), 3.61 (s, 3H), 3.28-3.20 (m, 2H), 2.92-2.68 (dd, 2H), 1.52-1.74 (m, 2H), 1.42 (s, 9H), 1.35-1.10 (m, 3H),

1. additionAfter addition
2. customto quench
3. customthe reaction
4. extractionThe aqueous layer was extracted with CH2Cl2 (3×100 mL)
5. washthe combined organic layers were washed with 10% citric acid (2×80 mL) and brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto give the crude product, which
10. customwas purified by column chromatography