2-(trifluoromethyl)pyrimidine-4-carboxylic acid synthesis

Yield: 68%

Reaction Conditions:

with lithium hydroxide monohydrate;water in methanol at 20; for 2 h;Inert atmosphere;

Steps:

2 Step 2 - 2-(Trifluoromethyl)pyrimidine-4-carboxylic acid
To a solution of methyl 2-(trifluoromethyl)pyrimidine-4-carboxylate (70.0 mg, 339 umol) in MeOH (4.00 mL) and H₂O (0.40 mL) was added LiOH^.H₂O (42.7 mg, 1.02 mmol). The mixture was stirred at 20 °C for 2 hrs. On completion, the reaction mixture was concentrated in vacuo to remove MeOH, then acid by addition 1 N HCl until the pH = 3-4, then extracted with EA (3 X 5 mL). The combined organic layer was washed with brine (2 X 10 mL), dried over anhydrous Na₂SO₄, filtered and concentrated in vacuo to give the title compound (45.0 mg, 68% yield) as a white solid.¹H NMR (400 MHz, DMSO-d6) d 9.29 (d, J = 5.2 Hz, 1H), 8.26 (d, J = 4.8 Hz, 1H).

References:

KYMERA THERAPEUTICS, INC.;MAINOLFI, Nello;JI, Nan;WEISS, Matthew M.;ZHENG, Xiaozhang;ZHANG, Yi;FLEMING, Paul R. WO2020/264499, 2020, A1 Location in patent:Paragraph 00920; 003053; 003056-003057