2,2,2-Trifluoroethanol → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (18 mg, 0.039 mmol), methyl 4-(7-amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)piperazine-2-carboxylate (Compound 287A, 6.0 mg, 0.020 mmol), trifluoroacetic acid (4.6 μL, 0.060 mmol) and 0.5 mL trifluoroethanol were mixed. The mixture was heated in microwave 105° C. for 30 minutes. Solvent was evaporated. To the crude solid was added, 0.1 mL THF, 0.1 mL methanol, 0.1 mL water and lithium hydroxide monohydrate (8.3 mg, 0.20 mmol). The mixture was stirred at room temperature overnight. The crude material was purified by MDP to obtain the title compound as a trifluoroacetic acid salt (1.1 mg, 7.9% yield). 1H NMR (400 MHz, methanol-d4) δ=1.28 (t, J=7.3 Hz, 6 H), 3.18 (s, 3 H), 3.21-3.24 (m, 1 H), 3.33 (d, J=21.7 Hz, 2 H), 3.37-3.43 (m, 2 H), 3.45-3.51 (m, 1 H), 3.55-3.61 (m, 2 H), 3.90 (s, 3 H), 4.06-4.11 (m, 4 H), 4.32-4.39 (m, 1 H), 4.44-4.59 (m, 2 H), 6.99 (d, J=7.8 Hz, 1 H), 7.09 (s, 1 H), 7.25 (d, J=8.8 Hz, 1 H), 7.75 (d, J=8.3 Hz, 1 H), 8.35 (s, 1 H), 8.49 (br. s., 1 H). MS (ES+): m/z 708.26 (100) [MH+]; HPLC: tR=0.77 min (UPLC, purity).

Provenance & Evidence