Hydrochloric Acid → Trifluoroacetic acid

참여 물질

반응 단계

To a degassed solution of the title compound from Example 3 Step A (24.0 mg, 0.038 mmol) in EtOAc (2 mL) was added platinum(IV) oxide (8.0 mg). The reaction mixture was fitted with a hydrogen balloon attached to a 3-way adapter. The reaction flask was then evacuated and back-filled with hydrogen. After this process was repeated three times, the reaction mixture was placed under a hydrogen atmosphere and was stirred vigorously. After 45 min, the reaction mixture was filtered through Celite, rinsing with EtOAc. The mixture was concentrated in vacuo and used without further purification: LCMS m/z 640.6 [M+H]+. To a solution of the hydrogenation product in 1,4-dioxane (2 mL) was added lithium hydroxide (1.0 mL, 2.0 M in water, 2.00 mmol), and the resulting mixture was stirred at 50° C. After 30 min, the reaction mixture was rendered acidic by addition of aqueous hydrochloric acid, then was diluted with 1,4-dioxane and passed through a 0.45 micron syringe filter. Purification by reverse phase HPLC (50 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 612.5 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.12 (d, J=8.0 Hz, 1H), 8.11 (s, 1H), 8.08 (t, J=8.0 Hz, 1H), 7.74 (dd, J=8.0, 1.5 Hz, 1H), 7.69 (d, J=7.5 Hz, 1H), 7.60 (d, J=8.5 Hz, 2H), 7.43 (d, J=8.5 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.26 (d, J=8.5 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 7.09 (t, J=8.5 Hz, 1H), 5.20 (s, 2H), 2.97-2.94 (m, 2H), 2.91-2.88 (m, 2H).

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