Hydrochloric Acid → Trifluoroacetic acid

HRID 1255161Notes

Reaction equation

HRID 1255161 reaction equation
[C:1]1([CH2:7][CH2:8][C:9]2[CH:42]=[CH:41][C:12]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:21]3[N:26]=[C:25]([N:27]4[C:31]([C:32]([F:35])([F:34])[F:33])=[C:30]([C:36]([O:38]CC)=[O:37])[CH:29]=[N:28]4)[CH:24]=[CH:23][CH:22]=3)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-:43].[Li+].Cl.[O:46]1CCOCC1>>[C:31]([OH:46])([C:32]([F:35])([F:34])[F:33])=[O:43].[C:1]1([CH2:7][CH2:8][C:9]2[CH:42]=[CH:41][C:12]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:21]3[N:26]=[C:25]([N:27]4[C:31]([C:32]([F:35])([F:33])[F:34])=[C:30]([C:36]([OH:38])=[O:37])[CH:29]=[N:28]4)[CH:24]=[CH:23][CH:22]=3)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 312751,4-Dioxane2×HCID 67159203Ethyl 1-[6-(2-{[4-(2-phenylethyl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 252331251-[6-(2-{[4-(2-Phenylethyl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid

Conditions

Temperature
60 °C

Procedure

To a solution of the title compound from Example 1 Step C (27.0 mg, 0.048 mmol) in 1,4-dioxane (2 mL) was added lithium hydroxide (1.0 mL, 2.0 M aqueous, 2.0 mmol), and the resulting mixture was stirred at 60° C. After 15 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 (30 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 544.4 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.25 (s, 1H), 8.14-8.07 (m, 2H), 7.74 (d, J=7.5 Hz, 1H), 7.69 (d, J=7.5 Hz, 1H), 7.42 (t, J=7.5 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 7.27-7.14 (m, 8H), 7.09 (t, J=8.0 Hz, 1H), 5.19 (s, 2H), 2.86 (app s, 4H).

Workup

  1. filtrationfilter
  2. customPurification by reverse phase HPLC (30 to 100% acetonitrile in water

Sources & evidence

ORD record
ord-8d15f1a163d84cf185640e091a810629
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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