反应详情

温度

0 °C

To a solution of (S)-tert-butyl 2-amino-3-cyclohexylpropyl(methyl)carbamate (165 mg, 0.61 mmol) and DIEA (3 mL) in anhydrous CH2Cl2 (10 mL) was added CDI (98 mg, 0.61 mmol) with ice bath. After addition, the mixture was stirred for 1 h at 0° C., followed by the addition of methyl 4-((R)-(3-chlorophenyl)((R)-piperidin-3-yl)methoxy)butanoate (165 mg, 0.51 mmol) in anhydrous CH2Cl2 (2 mL). The reaction mixture was allowed to warm to rt and stirred overnight. The reaction mixture was washed with water (10 mL) and the aqueous layer extracted with CH2Cl2 (15 mL×2), the combined organic layers was washed with saturated brine, dried over Na2SO4, filtered, then evaporated to give a residue, which was purified via preparative TLC to afford methyl 4-((R)—((R)-1-((S)-1-(tert-butoxycarbonyl(methyl)amino)-3-cyclohexylpropan-2-ylcarbamoyl)piperidin-3-yl)(3-chlorophenyl)methoxy)butanoate (70 mg, 22% yield). 1H NMR (CD3OD, 400 MHz) δ 7.34-7.28 (m, 3H), 7.19 (t, 1H), 4.25 (d, 1H), 4.11 (d, 1H), 3.95 (m, 2H), 3.64 (t, 3H), 3.27 (m, 1H), 3.10 (m, 1H), 2.87 (s, 2H), 2.69 (m, 2H), 2.43 (t, 1H), 1.84 (t, 2H), 1.72-1.52 (m, 6H), 1.45 (d, 9H), 1.39-1.22 (m, 10H), 1.14 (d, 1H), 0.97 (d, 2H), 0.85 (t, 1H).

1. additionAfter addition
2. temperatureto warm to rt
3. stirringstirred overnight
4. washThe reaction mixture was washed with water (10 mL)
5. extractionthe aqueous layer extracted with CH2Cl2 (15 mL×2)
6. washthe combined organic layers was washed with saturated brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customevaporated
10. customto give a residue, which
11. customwas purified via preparative TLC