Sodium Hydroxide → Trifluoroacetic acid

HRID 1255212Notes

Reaction equation

HRID 1255212 reaction equation
CC([O-:5])(C)C.[K+].[F:7][C:8]([F:24])([F:23])[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][OH:22])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1.F[C:26]1[C:31]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([N:38]3[C:42]([C:43]([F:46])([F:45])[F:44])=[C:41]([C:47]([O:49]CC)=[O:48])[CH:40]=[N:39]3)[N:33]=2)=[CH:30][CH:29]=[CH:28][N:27]=1.[OH-:52].[Na+]>O.C(#N)C.O1CCOCC1.CO.CN(C=O)C>[C:9]([OH:5])([C:8]([F:24])([F:23])[F:7])=[O:52].[F:46][C:43]([F:44])([F:45])[C:42]1[N:38]([C:34]2[N:33]=[C:32]([C:31]3[C:26]([O:22][CH2:21][C:18]4[CH:19]=[CH:20][C:15]([C:12]5[CH:11]=[CH:10][C:9]([C:8]([F:23])([F:24])[F:7])=[CH:14][CH:13]=5)=[CH:16][CH:17]=4)=[N:27][CH:28]=[CH:29][CH:30]=3)[CH:37]=[CH:36][CH:35]=2)[N:39]=[CH:40][C:41]=1[C:47]([OH:49])=[O:48]

Participants

11

Reactant 4

HCID 14798Sodium HydroxideHCID 22015014(4'-(Trifluoromethyl)-[1,1'-biphenyl]-4-yl)methanolHCID 23665647Potassium tert-butoxideHCID 67158682Ethyl 1-(2'-fluoro-2,3'-bipyridin-6-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 578259115-(Trifluoromethyl)-1-(2'-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-2,3'-bipyridin-6-yl)-1H-pyrazole-4-carboxylic acid

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Procedure

To a vial were added successively KOtBu (15.0 mg, 0.13 mmol), [4′-(trifluoromethyl)biphenyl-4-yl]methanol (US Patent 2004209936) (36.0 mg, 0.14 mmol) and DMF (0.3 mL). After 5 min, the title compound from Example 237 Step A (20.0 mg, 0.05 mmol) was added. After 30 min, the reaction mixture was treated with NaOH (0.1 mL, 3 N aqueous, 0.3 mmol), MeOH (0.1 mL) and 1,4-dioxane (0.1 mL) at 50° C. for 20 min. Reverse phase HPLC using a YMC C-18 column (65 to 100% acetonitrile in water, each with 0.1% v/v TFA) gave the title compound: LCMS m/z 584.9 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 8.44 (dd, J=7.6, 1.9 Hz, 1H), 8.31 (d, J=7.8 Hz, 1H), 8.27 (dd, J=4.9, 2.0 Hz, 1H), 8.20 (s, 1H), 7.94 (t, J=7.9 Hz, 1H), 7.69 (s, 4H), 7.62-7.53 (m, 5H), 7.10 (dd, J=7.5, 4.9 Hz, 1H), 5.63 (s, 2H).

Workup

  1. waitAfter 30 min

Sources & evidence

ORD record
ord-fd2cadc9e3304ea8bc0ff72b943fc8a8
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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