Methyl Acrylate → HCID 59458963, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)—N—((S)-1-(3-bromo-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)-phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide, prepared as described in Procedure 3, 62, 5 and 6, (500 mg, 0.82 mmol) in DMF (5 mL) at rt was added methyl acrylate (0.74 mL, 8.22 mmol), Pd2(dba)3 (75 mg, 0.082 mmol), tri-t-butyl phosphine (89 μL, 0.33 mmol), and cesium carbonate (536 mg, 1.64 mmol). The reaction mixture was degassed with argon and was heated at 100° C. for 4 h. The reaction mixture was poured into water and the aqueous phase extracted with ethyl acetate. The combined organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO chromatography (4 g column, 0-40% EtOAc/hexane) to yield (E)-methyl 3-(5-((R)-1-((R)-1,1-dimethylethylsulfinamido)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-fluorophenyl)acrylate as a white foam (485 mg, 96% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (d, J=16.42 Hz, 1H), 7.59 (dd, J=6.69, 2.15 Hz, 1H), 7.41 (m, 1H), 7.16 (m, 4H), 6.94 (dd, J=7.33, 1.77 Hz, 2H), 6.86 (d, J=8.84 Hz, 1H), 6.73 (t, J=4.93 Hz, 2H), 6.53 (d, J=16.17 Hz, 1H), 5.88 (m, 1H), 4.29 (s, 1H), 4.03 (d, J=12.38 Hz, 1H), 3.79 (s, 3H), 3.62 (d, J=12.38 Hz, 1H), 1.24 (m, 9H).

Provenance & Evidence