Hydrochloric Acid → 3'-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-4-carboxylic acid

HRID 530393Notes

Reaction equation

[OH-].[Li+].[F:3][C:4]([F:30])([F:29])[C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]2[CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([O:26]CC)=[O:25])=[CH:20][CH:19]=3)[CH:15]=[CH:16][CH:17]=2)[N:6]=1.Cl>C1COCC1.CO.[Cl-].[Na+].O>[F:30][C:4]([F:3])([F:29])[C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]2[CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([OH:26])=[O:25])=[CH:20][CH:19]=3)[CH:15]=[CH:16][CH:17]=2)[N:6]=1

Participants

Conditions

Temperature: 45 °C

Procedure

Lithium hydroxide (2 M, 0.374 mL, 0.749 mmol) was added to a solution of ethyl 3′-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-4-carboxylate in THF (1.99 mL) and methanol (0.99 mL) at room temperature, and then the mixture was heated at 45° C. for 6 hours. The reaction mixture was cooled to room temperature, neutralized with 10% aqueous HCl, diluted with brine, extracted with ethyl acetate (2×), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes+0.1% AcOH) to afford 3′-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-4-carboxylic acid as an off-white solid MS ESI calc'd. for C18H13F3N3O2 [M+H]+ 360, found 360. 1H NMR (500 MHz, CD3OD): δ 8.74 (s, 1H); 8.17 (s, 1H); 8.12 (d, J=7.9 Hz, 2H); 7.81-7.73 (m, 3H); 7.45 (t, J=7.9 Hz, 1H); 7.42-7.36 (m, 1H); 7.15 (d, J=4.5 Hz, 1H).

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionextracted with ethyl acetate (2×)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes+0.1% AcOH)

Sources & evidence

ORD record: ord-7faf3463f32546d78c6f73bb1e94e33a
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09353066B2

Reaction notes

Loading…