Sodium Carbonate → Trifluoroacetic acid

HRID 1255220Notes

Reaction equation

HRID 1255220 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:37])([F:36])[O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2[N:21]=[C:20]([N:22]3[C:26]([C:27]([F:30])([F:29])[F:28])=[C:25]([C:31]([O:33]CC)=[O:32])[CH:24]=[N:23]3)[CH:19]=[CH:18][CH:17]=2)=[CH:4][CH:3]=1.[F:38][C:39]([F:50])([F:49])[C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1.[C:51]([O-:54])([O-])=[O:52].[Na+].[Na+]>CC#N>[C:51]([OH:54])([C:27]([F:30])([F:29])[F:28])=[O:52].[F:37][C:8]([F:36])([C:5]1[CH:6]=[CH:7][C:2]([C:43]2[CH:44]=[CH:45][C:40]([C:39]([F:50])([F:49])[F:38])=[CH:41][CH:42]=2)=[CH:3][CH:4]=1)[O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[N:21]=[C:20]([N:22]2[C:26]([C:27]([F:29])([F:30])[F:28])=[C:25]([C:31]([OH:33])=[O:32])[CH:24]=[N:23]2)[CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 86633499Ethyl 1-(6-{2-[(4-bromophenyl)(difluoro)methoxy]phenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 252313621-[6-(2-{Difluoro[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of the title compound from Example 300 Step A (50.0 mg, 0.086 mmol), 4-trifluoromethylphenylboronic acid (35 mg, 0.18 mmol), trans-dichlorobis(triphenylphosphine) palladium (II) (9.0 mg, 0.013 mmol), Na2CO3 (0.1 mL, 2.0 M aqueous, 0.2 mmol), and MeCN (1 mL) was stirred at 90° C. for 35 min. The crude mixture was dried concentrated in vacuo. Treatment with a mixture of 0.1 mL each of 3 N NaOH, dioxane and MeOH at 50° C. for 10 min, followed by reverse phase HPLC using a YMC C-18 column (65 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 599.9 [M−F]+; 1H NMR (500 MHz, acetone-d6) δ 8.34 (m, 2H), 8.03 (d, J=7.6 Hz, 1H), 7.99 (d, J=8.2 Hz, 1H), 7.95-7.78 (m, 7H), 7.69 (d, J=8.5 Hz, 2H), 7.62 (m, 2H).

Workup

  1. dry with materialThe crude mixture was dried
  2. concentrationconcentrated in vacuo
  3. additionTreatment with a mixture of 0.1 mL each of 3 N NaOH, dioxane and MeOH at 50° C. for 10 min

Sources & evidence

ORD record
ord-2516cbb24b7847b9b300ffa6c5a9b6f2
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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