Sodium Carbonate → Trifluoroacetic acid

HRID 1255218Notes

Reaction equation

HRID 1255218 reaction equation
Br[C:2]1[CH:36]=[CH:35][C:5]([CH2:6][S:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][C:9]=2[C:15]2[N:20]=[C:19]([N:21]3[C:25]([C:26]([F:29])([F:28])[F:27])=[C:24]([C:30]([O:32]CC)=[O:31])[CH:23]=[N:22]3)[CH:18]=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.[F:37][C:38]([F:49])([F:48])[C:39]1[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=1.[F-].[Cs+].[C:52](=[O:55])([O-])[O-:53].[Na+].[Na+].[OH-].[Na+]>C(#N)C.CO>[C:52]([OH:53])([C:26]([F:29])([F:28])[F:27])=[O:55].[CH3:14][C:11]1[CH:12]=[CH:13][C:8]([S:7][CH2:6][C:5]2[CH:35]=[CH:36][C:2]([C:42]3[CH:43]=[CH:44][C:39]([C:38]([F:49])([F:48])[F:37])=[CH:40][CH:41]=3)=[CH:3][CH:4]=2)=[C:9]([C:15]2[N:20]=[C:19]([N:21]3[C:25]([C:26]([F:28])([F:29])[F:27])=[C:24]([C:30]([OH:32])=[O:31])[CH:23]=[N:22]3)[CH:18]=[CH:17][CH:16]=2)[CH:10]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 25953Cesium fluorideHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 67159377HCID 67159377, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 25231361HCID 25231361, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A solution of the title compound from Example 243 Step D (24 mg, 0.04 mmol), 4-(trifluoromethyl)phenylboronic acid (10.4 mg, 0.06 mmol), trans dichlorobis(triphenylphosphine) palladium (II) (8.9 mg, 0.01 mmol), and cesium fluoride (19 mg, 0.13 mmol), in acetonitrile (0.5 mL) was stirred for 5 min, then sodium carbonate (0.13 mL, 1.0 M aqueous, 0.13 mmol) was added. The resulting mixture was stirred at 90° C. After 30 minutes, the reaction mixture was allowed to cool to ambient temperature, then was quenched with water and extracted with 30% ethyl acetate in hexane. The organic phase was dried over sodium sulfate, passed through a silica pad, eluting with DCM, and concentrated in vacuo. To a solution of the crude reaction product in 1,4-dioxane (0.200 mL) and methanol (0.030 mL) was added sodium hydroxide (0.040 mL, 1.0 M aqueous, 0.040 mmol), and the reaction mixture was then heated at 50° C. After 15 min, the reaction mixture was allowed to cool to ambient temperature. The reaction mixture was concentrated in vacuo then acidified with TFA (2 N in DMSO). Purification by reverse phase HPLC (65 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 614.9 [M+H]+; 1H NMR (500 MHz, CD2Cl2) δ 8.13 (s, 1H), 7.96 (t, J=7.9 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.69-7.65 (m, 4H), 7.60 (d, J=8.0 Hz, 1H), 7.46 (d, J=8.0 Hz, 2H), 7.41 (d, J=8.0 Hz, 1H), 7.37 (s, 1H), 7.18 (d, J=8.2 Hz, 3H), 3.94 (s, 2H), 2.36 (s, 3H).

Workup

  1. temperatureto cool to ambient temperature
  2. customwas quenched with water
  3. extractionextracted with 30% ethyl acetate in hexane
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. washeluting with DCM
  6. concentrationconcentrated in vacuo
  7. customTo a solution of the crude reaction product in 1,4-dioxane (0.200 mL)
  8. temperaturethe reaction mixture was then heated at 50° C
  9. waitAfter 15 min
  10. temperatureto cool to ambient temperature
  11. concentrationThe reaction mixture was concentrated in vacuo
  12. customPurification by reverse phase HPLC (65 to 100% acetonitrile in water

Sources & evidence

ORD record
ord-10d4042958f840aca10bf5c90f3fb9aa
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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