Hydrochloric Acid → Trifluoroacetic acid

HRID 1255182Notes

Reaction equation

HRID 1255182 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:41]=[CH:40][C:11]([CH2:12][O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]3[N:25]=[C:24]([N:26]4[C:30]([C:31]([F:34])([F:33])[F:32])=[C:29]([C:35]([O:37]CC)=[O:36])[CH:28]=[N:27]4)[CH:23]=[CH:22][CH:21]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[OH-:42].[Li+].Cl.[O:45]1CCOCC1>>[C:30]([OH:45])([C:31]([F:34])([F:33])[F:32])=[O:42].[O:1]=[C:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:9]=[CH:10][C:11]([CH2:12][O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]3[N:25]=[C:24]([N:26]4[C:30]([C:31]([F:34])([F:33])[F:32])=[C:29]([C:35]([OH:37])=[O:36])[CH:28]=[N:27]4)[CH:23]=[CH:22][CH:21]=3)=[CH:40][CH:41]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 312751,4-Dioxane2×HCID 67159542Ethyl 1-[6-(2-{[4-(4-oxocyclohexyl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 252334631-[6-(2-{[4-(4-Oxocyclohexyl)benzyl]oxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid

Conditions

Temperature
50 °C

Procedure

To a solution of the title compound from Example 10 Step E (20.0 mg, 0.035 mmol) in 1,4-dioxane (1.0 mL) was added lithium hydroxide (0.500 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 95% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 536.0 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.30 (s, 1H), 8.14 (d, J=7.5 Hz, 1H), 8.11 (t, J=7.5 Hz, 1H), 7.73-7.70 (m, 2H), 7.43 (t, J=8.0 Hz, 1H), 7.35 (d, J=8.0 Hz, 2H), 7.29-7.26 (m, 3H), 7.09 (t, J=7.5 Hz, 1H), 5.21 (s, 2H), 3.07-3.02 (m, 1H), 2.57 (td, J=14.0, 5.5 Hz, 2 H), 2.26-2.24 (m, 2H), 2.05-2.03 (m, 2H), 1.90-1.82 (m, 2H).

Workup

  1. filtrationfilter
  2. customPurification by reverse phase HPLC (40 to 95% acetonitrile in water

Sources & evidence

ORD record
ord-d97735a9e1d847038881f70c53a8fce5
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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