2,2,2-Trifluoroethanol → Trifluoroacetic acid

Participants

Reaction Steps

A mixture of diethyl(4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (30.0 mg, 0.0661 mmol), methyl 1-(7-amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)piperidine-4-carboxylate (Compound 256A, 20.0 mg, 0.0659 mmol), trifluoroacetic acid (15.2 uL, 0.198 mmol) and trifluoroethanol (1.0 mL, 14 mmol) was irradiated in microwave reactor at 105° C. for 30 minutes. The crude mixture was concentrated to dryness, taken up in THF (0.1 mL), methanol (0.1 mL) and treated with a solution of lithium hydroxide monohydrate (27.7 mg, 0.659 mmol) in water (0.1 mL). The mixture was stirred at room temperature overnight. The crude was purified by MDP to obtain the title compound as a trifluoroacetic acid salt (7.2 mg, 15.5% yield). 1H NMR (400 MHz, DMSO-d6) δ=1.29 (t, J=7.1 Hz, 6H), 1.83-1.97 (m, 2H), 2.03-2.14 (m, 2H), 2.46-2.57 (m, 1H), 2.93 (t, J=10.5 Hz, 2H), 3.18 (s, 3H), 3.34 (d, J+ 18.7 Hz, 2H), 3.40 (d, J=12.1 Hz, 2H), 3.90 (s, 3H), 4.10 (quin, J=7.3 Hz, 4H), 4.52 (s, 2H), 6.94-7.01 (m, 1H), 7.09-7.17 (m, 2H), 7.67 (d, J=8.1 Hz, 1H), 8.27-8.47 (m, 2H). MS (ES+): m/z 707.19 (100) [MH+]; HPLC: tR=1.01 min (UPLC, purity).

Provenance & Evidence