Methanol → Trifluoroacetic acid

HRID 2207422Notes

Reaction equation

[OH-:1].[Na+].[CH3:3][OH:4].[CH3:5][C:6]([CH3:37])([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[C:23]([NH:25][C:26]3[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][N:27]=3)[CH:22]=[C:21]([CH3:36])[CH:20]=2)=[CH:15][N:14]=1)[C:7]([O:9]CC)=[O:8]>C1COCC1>[CH3:5][C:6]([CH3:37])([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[C:23]([NH:25][C:26]3[N:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:29]=[CH:28][N:27]=3)[CH:22]=[C:21]([CH3:36])[CH:20]=2)=[CH:15][N:14]=1)[C:7]([OH:9])=[O:8].[C:3]([OH:4])([C:32]([F:35])([F:34])[F:33])=[O:1]

Participants

Conditions

Temperature: 50 °C

Procedure

1 M NaOH (0.230 mL, 0.230 mmol) and MeOH (0.400 mL) were added to a solution of ethyl 2,2-dimethyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]propanoate (20.7 mg, 0.045 mmol) in THF (0.50 mL) and the reaction mixture was heated to 50° C. for 2 hours. The reaction was cooled to room temperature, concentrated under reduced pressure and the residue was directly purified by reverse phase HPLC to afford 2,2-dimethyl-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]propanic acid as a TFA salt. C22H22F3N4O2 [M+H]+ 431. found 431. 1H NMR (500 MHz, DMSO-d6) δ 10.28 (s, 1H), 8.83 (d, J=4.9 Hz, 1H), 8.79 (s, 1H), 8.17-8.04 (m, 1H), 7.95 (s, 1H), 7.57 (s, 1H), 7.44 (d, 1H), 7.27 (d, J=4.9 Hz, 1H), 7.22 (s, 1H), 3.05 (s, 2H), 2.36 (s, 3H), 1.14 (s, 6H).

Workup

temperatureThe reaction was cooled to room temperature
concentrationconcentrated under reduced pressure
customthe residue was directly purified by reverse phase HPLC

Sources & evidence

ORD record: ord-c389253826e54681bac138d26fa73c9a
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376418B2

Reaction notes

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