Hydrochloric Acid → Trifluoroacetic acid

HRID 1255193Notes

Reaction equation

HRID 1255193 reaction equation
[CH3:1][C:2]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:3]=1[CH2:4][O:5][C:6]1[C:11]([CH3:12])=[CH:10][CH:9]=[CH:8][C:7]=1[C:13]1[N:18]=[C:17]([N:19]2[C:23]([C:24]([F:27])([F:26])[F:25])=[C:22]([C:28]([O:30]CC)=[O:29])[CH:21]=[N:20]2)[CH:16]=[CH:15][CH:14]=1.[OH-:38].[Li+].Cl.[O:41]1CCOCC1>>[C:23]([OH:41])([C:24]([F:27])([F:26])[F:25])=[O:38].[CH3:1][C:2]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][C:3]=1[CH2:4][O:5][C:6]1[C:11]([CH3:12])=[CH:10][CH:9]=[CH:8][C:7]=1[C:13]1[N:18]=[C:17]([N:19]2[C:23]([C:24]([F:25])([F:26])[F:27])=[C:22]([C:28]([OH:30])=[O:29])[CH:21]=[N:20]2)[CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 312751,4-Dioxane2×HCID 67159648Ethyl 1-(6-{2-[(2,4-dimethylbenzyl)oxy]-3-methylphenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 252315251-(6-{2-[(2,4-Dimethylbenzyl)oxy]-3-methylphenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid

Conditions

Temperature
50 °C

Procedure

To a solution of the title compound from Example 15 Step C (12.0 mg, 0.023 mmol) in 1,4-dioxane (1.5 mL) was added lithium hydroxide (0.5 mL, 2.0 M in water, 1.00 mmol), and the resulting mixture was stirred at 50° C. After 30 min, 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 (40 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 482.8 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.30 (s, 1H), 8.08 (t, J=8.0 Hz, 1H), 7.95 (d, J=8.0 Hz, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.45 (dd, J=8.0, 1.5 Hz, 1H), 7.35-7.32 (m, 1H), 7.18 (t, J=7.5 Hz, 1H), 6.91-6.86 (m, 3H), 4.52 (s, 2H), 2.27 (s, 3H), 2.21 (s, 3H), 2.06 (s, 3H).

Workup

  1. filtrationfilter
  2. customPurification by reverse phase HPLC (40 to 100% acetonitrile in water

Sources & evidence

ORD record
ord-bc240a67dd214a179cd73c6d4895c929
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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