Lithium Hydroxide → (1-benzyl-3-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone

HRID 623790Notes

Reaction equation

HRID 623790 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]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-].Br[C:38]1[CH:43]=[CH:42][C:41]([O:44][C:45]([F:48])([F:47])[F:46])=[CH:40][C:39]=1[F:49].[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:15])([F:14])[F:16])=[C:11]([CH3:17])[C:10]([C:38]2[CH:43]=[CH:42][C:41]([O:44][C:45]([F:48])([F:47])[F:46])=[CH:40][C:39]=2[F:49])=[C:9]1[C:27]([N:29]1[CH2:30][CH2:31][O:32][CH2:33][CH2:34]1)=[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 220652111-Bromo-2-fluoro-4-(trifluoromethoxy)benzeneHCID 86711876(1-benzyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone

Product 1

HCID 86711875(1-benzyl-3-(2-fluoro-4-(trifluoromethoxy)phenyl)-4-methyl-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanoneYield 66.8%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Under an nitrogen atmosphere (1-benzyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1H-pyrrol-2-yl)(morpholino)methanone (50 mg, 0.106 mmol) was dissolved in DMF (0.5 mL) and LiOH (2 mg, 0.106 mmol), bis(tri-tert-butylphosphine)palladium (0) (3 mg, 0.007 mmol) and 1-bromo-2-fluoro-4-(trifluoromethoxy)benzene (24 mg, 0.096 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-262 (34 mg, 66.8%).

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-05a82a635b0b4865a4e29a694451b4af
Source dataset
uspto-grants-2016_04
Patent number
US09302988B2

Reaction notes

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