Phosgene → (S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid 2-(di-tert-butoxy-phosphoryloxy)-propyl ester

Participants

Reaction Steps

To a solution of (S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one ((S)-II) (720 mg, 2 mmol) in dichloromethane was dropped in phosgene (2.2 mL, 20% solution in toluene, 4 mmol) and pyridine (0.6 mL). The resulting chloroformate (S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-indole-1-carbonyl chloride ((S)-VI) was stirred at room temperature under N2 atmosphere over night. To this reaction mixture was dropped in another 0.6 mL of pyridine, followed by the addition of phosphoric acid di-tert-butyl ester 3-hydroxy-propyl ester (1.55 g, ˜5.78 mmol), the preparation of which is given below. The resulting mixture was stirred at room temperature for another hour, was diluted with dichloromethane and washed with water. The organic layer was dried over Na2SO4 and condensed by evaporator. The residue was chromatographed on a silica gel flash column packed with ethyl acetate:hexane (v/v, 4:1) and eluted with ethyl acetate:hexane (v/v, 4:1˜2:1) to afford the title compound (818 mg, 63%). 1H NMR (CDCl3, 500 MHz) δ 10.06 (s, 1H), 8.31 (s, 1H), 7.78 (t, 1H), 7.43 (d, 1H), 7.35 (dd, 1H), 7.27 (d, 1H), 6.76 (dd, 1H), 4.59 (m, 2H), 4.16 (m, 2H), 3.52 (s, 3H), 2.18 (m, 2H), 1.48 (s, 18H); LC-MS, 654.1 (MH+).

Provenance & Evidence