1-Chloro-2-fluoro-4-isocyanato-benzene → (4-chloro-3-fluoro-phenyl)-carbamic acid (S)-1-[(R)-2-(3-chlorophenyl)-morpholin-4-ylmethyl]-2,2,2-trifluoro-ethyl ester hydrochloride

Participants

Reaction Steps

(S)-3-((R)-2-(3-chlorophenyl)morpholino)-1,1,1-trifluoropropan-2-ol (59.5 mg, 192 μmol), TEA (26.8 μL, 192 μmol) and 1-chloro-2-fluoro-4-isocyanatobenzene (32.9 mg, 192 μmol) were combined in 2 mL of acetonitrile and stirred at room temperature overnight. The solution was purified by reverse phase column chromatography (50-100% acetonitrile in water). The desired fractions were pooled, treated with 5 drops of conc. HCl and the solution lyophilized to afford (4-chloro-3-fluoro-phenyl)-carbamic acid (S)-1-[(R)-2-(3-chlorophenyl)-morpholin-4-ylmethyl]-2,2,2-trifluoro-ethyl ester hydrochloride (56 mg, 56%) as a white solid. (M+H)+=481 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.81 (t, J=11.14 Hz, 1H) 3.00 (t, J=10.39 Hz, 1H) 3.16 (d, J=13.22 Hz, 1H) 3.44 (d, J=11.71 Hz, 1H) 3.56-3.79 (m, 2H) 4.20 (dd, J=13.22, 3.02 Hz, 1H) 4.36-4.59 (m, 1H) 5.55 (d, J=9.82 Hz, 1H) 5.70 (d, J=3.02 Hz, 1H) 7.17 (d, J=8.69 Hz, 1H) 7.29-7.44 (m, 5H) 7.50 (dd, J=10.77, 2.08 Hz, 1H) 8.82 (br. s., 1H).

Provenance & Evidence