Ethylamine → HCID 178465144, compound

Temperature

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)

ORD record

ord-3bb037af37b5494097ea42ae903f68b5

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07781426B2