Lithium Hydroxide → 1-Benzyl-N,4-dimethyl-N-neopentyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxamide

HRID 623783

Reaction equation

HRID 623783 reaction equation
[CH2:1]([N:8]1[C:12]([C:13]([F:16])([F:15])[F:14])=[C:11]([CH3:17])[C:10](B2OC(C)(C)C(C)(C)O2)=[C:9]1[C:27]([N:29]([CH3:35])[CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-].Br[C:39]1[CH:44]=[CH:43][C:42]([O:45][CH2:46][C:47]([F:50])([F:49])[F:48])=[CH:41][CH:40]=1.[OH-].[Na+]>CN(C=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH2:1]([N:8]1[C:12]([C:13]([F:16])([F:14])[F:15])=[C:11]([CH3:17])[C:10]([C:39]2[CH:40]=[CH:41][C:42]([O:45][CH2:46][C:47]([F:48])([F:49])[F:50])=[CH:43][CH:44]=2)=[C:9]1[C:27]([N:29]([CH3:35])[CH2:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 229138831-Bromo-4-(2,2,2-trifluoroethoxy)benzeneHCID 867118691-benzyl-N,4-dimethyl-N-neopentyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxamide

Product 1

HCID 867118681-Benzyl-N,4-dimethyl-N-neopentyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxamideYield 89.7%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Under an nitrogen atmosphere 1-benzyl-N,4-dimethyl-N-neopentyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxamide (106 mg, 0.216 mmol) was dissolved in DMF (1 mL) and LiOH (4 mg, 0.216 mmol), bis(tri-tert-butylphosphine)palladium (0) (6 mg, 0.014 mmol) and 1-bromo-4-(2,2,2-trifluoroethoxy)benzene (50 mg, 0.196 mmol) were subsequently added. The reaction mixture was stirred at 80° C. under microwave irridation for 1 h. The mixture was cooled to RT and the reaction was stopped by addition of 1M NaOH solution (2 mL). The crude product was extracted with EtOAc (2×3 mL) and the combined organic layers were washed with water (3×1 mL), dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The crude mass was purified by flash chromatography to give SC-260 (95 mg, 89.7%).

Workup

  1. temperatureThe mixture was cooled to RT
  2. extractionThe crude product was extracted with EtOAc (2×3 mL)
  3. washthe combined organic layers were washed with water (3×1 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customThe crude mass was purified by flash chromatography

Sources & evidence

ORD record
ord-193d210bbf4f41e9aa40e1f8946886ab
Source dataset
uspto-grants-2016_04
Patent number
US09302988B2

Linked notes

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