反应详情

To a stirred solution of ethyl [trans-4-({ethyl[2-formyl-4-(trifluoromethyl)phenyl]amino}methyl)cyclohexyl]acetate (Step A; 153 mg; 0.38 mmol) in EtOH (1 mL) was added sodium borohydride (7.3 mg; 0.19 mmol). The reaction stirred at room temperature for 1 h and was concentrated in vacuo. The residue was redissolved in EtOAc (10 mL) and washed with sat. NH4Cl (10 mL). The aqueous layer was re-extracted with EtOAc (2×10 mL) and the combined organic layers were washed with H2O and brine (10 mL each), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-25% EtOAc/hexanes gradient) to afford ethyl [trans-4-({ethyl[2-(hydroxymethyl)-4-(trifluoromethyl)phenyl]amino}methyl)cyclohexyl]acetate as a yellow oil. LCMS=402.2 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 7.56-7.54 (m, 2 H), 7.29-7.26 (m, 1 H), 4.85 (s, 2 H), 4.13 (q, J=7.1 Hz, 2 H), 3.10-3.02 (m, 2 H), 2.91-2.85 (m, 2 H), 2.17 (d, J=6.9 Hz, 2 H), 1.84-1.70 (m, 4 H), 1.57-1.44 (m, 2 H), 1.39-1.31 (m, 1 H), 1.26 (t, J=7.1 Hz, 3 H), 1.08-1.04 (m, 3 H), 1.01-0.93 (m, 3 H).

1. concentrationwas concentrated in vacuo
2. dissolutionThe residue was redissolved in EtOAc (10 mL)
3. washwashed with sat. NH4Cl (10 mL)
4. extractionThe aqueous layer was re-extracted with EtOAc (2×10 mL)
5. washthe combined organic layers were washed with H2O and brine (10 mL each)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by flash silica gel chromatography (0-25% EtOAc/hexanes gradient)