Hydrochloric Acid → Trifluoroacetic acid

HRID 1255164Notes

Reaction equation

HRID 1255164 reaction equation
[F:1][C:2]([F:44])([F:43])[C:3]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=4)=[CH:24][CH:23]=3)[N:9]=2)[N:6]=[CH:5][C:4]=1[C:38]([O:40]CC)=[O:39].[OH-:45].[Li+].Cl.[O:48]1CCOCC1>>[C:3]([OH:48])([C:2]([F:44])([F:43])[F:1])=[O:45].[F:44][C:2]([F:1])([F:43])[C:3]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]([C:28]4[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:30][CH:29]=4)=[CH:26][CH:27]=3)[N:9]=2)[N:6]=[CH:5][C:4]=1[C:38]([OH:40])=[O:39]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 312751,4-Dioxane2×HCID 86633489Ethyl 5-(trifluoromethyl)-1-[6-(2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)pyridin-2-yl]-1H-pyrazole-4-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 252331265-(Trifluoromethyl)-1-[6-(2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)pyridin-2-yl]-1H-pyrazole-4-carboxylic acid

Conditions

Temperature
50 °C

Procedure

To a solution of the title compound from Example 2 Step B (ca. 0.073 mmol) in 1,4-dioxane (0.5 mL) was added lithium hydroxide (0.50 mL, 2.0 M in water, 1.00 mmol), and the resulting mixture was stirred at 50° C. After 2 h, the reaction mixture was rendered acidic by addition of aqueous hydrochloric acid, then was diluted with 1,4-dioxane and passed through a 0.45 micron syringe filter. Purification by reverse phase HPLC (50 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 584.1 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.30 (s, 1H), 8.18 (d, J=8.0 Hz, 1H), 8.14 (t, J=8.0 Hz, 1H), 7.88 (d, J=8.0 Hz, 2H), 7.80 (d, J=8.0 Hz, 2H), 7.75-7.71 (m, 4H), 7.56 (d, J=8.0 Hz, 2H), 7.46-7.43 (m, 1H), 7.30 (d, J=7.5 Hz, 1H), 7.11 (t, J=7.5 Hz, 1H), 5.32 (s, 2H).

Workup

  1. filtrationfilter
  2. customPurification by reverse phase HPLC (50 to 100% acetonitrile in water

Sources & evidence

ORD record
ord-f239249ca43d402692c0c2102c59376c
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

Loading…