Lithium Hydroxide → 1-[4-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylate (38 mg, 0.08 mmol) in tetrahydrofuran (0.5 mL) and methanol (0.5 mL) was added 1M aqueous lithium hydroxide (0.5 mL, 0.5 mmol). The reaction was heated to 50° C. for 2 hours. The mixture was then cooled to room temperature, diluted with 2-methyltetrahydrofuran (30 mL), and washed with 0.1N aqueous hydrochloride acid (30 mL) and brine (30 mL). The aqueous fractions were further extracted with 2-methyltetrahydrofuran (30 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure to provide 1-[4-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]piperidine-4-carboxylic acid (36 mg, 0.08 mmol, quantitative) as a light blue solid. MS APCI: [M+H]+ m/z 450.1. 1H NMR (400 MHz, DMSO): δ 10.23 (s, 1H); 8.82 (d, J=4.9 Hz, 1H); 8.38 (s, 1H); 7.61 (d, J=7.8 Hz, 1H); 7.50 (d, J=7.8 Hz, 1H); 7.32 (t, J=7.8 Hz, 1H); 7.27 (d, J=5.0 Hz, 1H); 7.15 (s, 1H); 6.65 (s, 2H); 3.93 (d, J=12.3 Hz, 2H); 3.22-3.08 (m, 2H); 1.95 (d, J=13.1 Hz, 2H); 1.65 (d, J=14.4 Hz, 2H). rhSyk=++.

Provenance & Evidence