Hydrochloric Acid → Trifluoroacetic acid

HRID 1255210Notes

Reaction equation

HRID 1255210 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25](OS(C(F)(F)F)(=O)=O)=[CH:24][CH:23]=3)[N:9]=2)[N:6]=[CH:5][C:4]=1[C:36]([O:38]CC)=[O:37].[F:43][C:44]([F:55])([F:54])[C:45]1[CH:50]=[CH:49][C:48](B(O)O)=[CH:47][CH:46]=1.[C:56](=[O:59])([O-])[O-:57].[Na+].[Na+].[OH-].[Li+].Cl>O1CCOCC1.C(#N)C>[C:56]([OH:57])([C:2]([F:42])([F:41])[F:1])=[O:59].[F:41][C:2]([F:42])([F:1])[C:3]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH2:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]([C:48]4[CH:49]=[CH:50][C:45]([C:44]([F:55])([F:54])[F:43])=[CH:46][CH:47]=4)=[CH:26][CH:27]=3)[N:9]=2)[N:6]=[CH:5][C:4]=1[C:36]([OH:38])=[O:37]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 86633496HCID 86633496, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 58270185HCID 58270185, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
50 °C

Procedure

A vial was charged with the title compound from Example 236 Step C (60.0 mg, 0.098 mmol), 4-trifluoromethylphenyl boronic acid (24.2 mg, 0.127 mmol), and trans-dichlorobis(triphenylphosphine) palladium (II) (6.9 mg, 0.010 mmol). Acetonitrile (0.400 mL) and sodium carbonate (0.244 mL, 1.0 M aqueous, 0.244 mmol) were added, and the mixture was degassed with nitrogen. The vial was then capped and placed in a pre-heated oil bath (70° C.). After 15 h, the mixture was diluted with water and DCM and the organic phase was filtered through a short pad of silica gel and Celite with DCM, then was concentrated in vacuo: LCMS m/z 610.4 [M+H]+. To a solution of the unpurified Suzuki product in 1,4-dioxane (2.0 mL) was added lithium hydroxide (1.0 mL, 2.0 M in water, 2.00 mmol), and the resulting mixture was stirred at 50° C. After 1 h, 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 (60 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 582.4 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.34 (s, 1H), 8.20 (t, J=8.0 Hz, 1H), 7.82-7.73 (m, 6H), 7.50 (d, J=8.0 Hz, 2H), 7.44-7.34 (m, 4H), 6.99 (d, J=8.0 Hz, 2H), 2.97-2.93 (m, 2H), 2.78-2.74 (m, 2H).

Workup

  1. customthe mixture was degassed with nitrogen
  2. customThe vial was then capped
  3. customplaced in a pre-heated oil bath
  4. custom(70° C.)
  5. additionthe mixture was diluted with water and DCM
  6. filtrationthe organic phase was filtered through a short pad of silica gel and Celite with DCM
  7. concentrationwas concentrated in vacuo
  8. waitAfter 1 h
  9. filtrationfilter
  10. customPurification by reverse phase HPLC (60 to 100% acetonitrile in water

Sources & evidence

ORD record
ord-1faf2c6660584959a6a20c7cb663752c
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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