反应详情

温度

0 °C

To a stirred solution of trans-4-(2-ethoxy-2-oxoethyl)-cyclohexanecarboxylic acid (Intermediate 6; 800 mg; 3.74 mmol) in CH2Cl2 (5 mL) was added oxalyl chloride (4.7 mL; 9.35 mmol), followed by a drop of DMF. After 3 h, the reaction was concentrated in vacuo, redissolved in THF (4 mL) and added dropwise to a stirred solution of ethylamine (2.0 M; 1.87 mL; 3.74 mmol) in THF (4 mL) at 0° C. Triethylamine (521 mL; 3.74 mmol) was added and the reaction stirred at 0° C. for 1 h. The reaction was quenched with H2O (25 mL) and extracted with EtOAc (3×50 mL). The combined extracted were washed with H2O and brine (25 mL each), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-75% EtOAc/hexanes gradient) to afford ethyl{trans-4-[(ethylamino)carbonyl]cyclohexyl}acetate as a white solid. LCMS=242.2 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 5.40 (s, 1 H), 4.14 (q, J=7.1 Hz, 2 H), 3.33-3.28 (m, 2 H), 2.21 (d, J=7.1 Hz, 2 H), 2.02 (tt, J=12.2, 3.4 Hz, 1 H), 1.94-1.78 (m, 5 H), 1.51 (qd, J=12.9, 3.2 Hz, 2 H), 1.27 (t, J=7.1 Hz, 3 H), 1.15 (t, J=7.3 Hz, 3 H), 1.07 (qd, J=12.8, 3.2 hz, 2 H).

1. concentrationthe reaction was concentrated in vacuo
2. dissolutionredissolved in THF (4 mL)
3. customThe reaction was quenched with H2O (25 mL)
4. extractionextracted with EtOAc (3×50 mL)
5. extractionThe combined extracted
6. washwere washed with H2O and brine (25 mL each)
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by flash silica gel chromatography (0-75% EtOAc/hexanes gradient)