Sodium Carbonate → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

A solution of the title compound from Example 243 Step D (24 mg, 0.04 mmol), 4-(trifluoromethyl)phenylboronic acid (10.4 mg, 0.06 mmol), trans dichlorobis(triphenylphosphine) palladium (II) (8.9 mg, 0.01 mmol), and cesium fluoride (19 mg, 0.13 mmol), in acetonitrile (0.5 mL) was stirred for 5 min, then sodium carbonate (0.13 mL, 1.0 M aqueous, 0.13 mmol) was added. The resulting mixture was stirred at 90° C. After 30 minutes, the reaction mixture was allowed to cool to ambient temperature, then was quenched with water and extracted with 30% ethyl acetate in hexane. The organic phase was dried over sodium sulfate, passed through a silica pad, eluting with DCM, and concentrated in vacuo. To a solution of the crude reaction product in 1,4-dioxane (0.200 mL) and methanol (0.030 mL) was added sodium hydroxide (0.040 mL, 1.0 M aqueous, 0.040 mmol), and the reaction mixture was then heated at 50° C. After 15 min, the reaction mixture was allowed to cool to ambient temperature. The reaction mixture was concentrated in vacuo then acidified with TFA (2 N in DMSO). Purification by reverse phase HPLC (65 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 614.9 [M+H]+; 1H NMR (500 MHz, CD2Cl2) δ 8.13 (s, 1H), 7.96 (t, J=7.9 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.69-7.65 (m, 4H), 7.60 (d, J=8.0 Hz, 1H), 7.46 (d, J=8.0 Hz, 2H), 7.41 (d, J=8.0 Hz, 1H), 7.37 (s, 1H), 7.18 (d, J=8.2 Hz, 3H), 3.94 (s, 2H), 2.36 (s, 3H).

Provenance & Evidence