Water → HCID 90407166, compound

HRID 1404176Notes

Reaction equation

HRID 1404176 reaction equation
Br[C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=2)[C:3]=1[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:18]([F:29])[C:17]=1[F:30].O.[CH3:32][N:33](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([N:4]2[CH:5]=[CH:6][C:2]([C:32]#[N:33])=[C:3]2[CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:18]([F:29])[C:17]=2[F:30])=[CH:8][CH:9]=1

Participants

7

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 90406743HCID 90406743, compound

Product 1

HCID 90407166HCID 90407166, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A solution of ethyl 3-(4-((3-bromo-1-(4-chlorophenyl)-1H-pyrrol-2-yl)methoxy)-2,3-difluorophenyl)propanoate (90 mg, 0.18 mmol, 1 eq), zinc cyanide (64 mg, 0.54 mmol, 3 eq), 1,1′-bis(diphenylphosphino)ferrocene (10 mg, 0.018 mmol, 0.1 eq), Pd2(dba)3 (16.5 mg, 0.018 mmol, 0.1 eq) in DMF (1.4 mL) under N2 was heated at 130° C. overnight in a vial. To the resulting mixture was added water, the aqueous was extracted with DCM, dried over MgSO4 and concentrated. The resulting residue was purified by flash chromatography (12 g column) eluting with 10 to 30% EtOAc/heptane to yield ethyl 3-(4-((1-(4-chlorophenyl)-3-cyano-1H-pyrrol-2-yl)methoxy)-2,3-difluorophenyl)propanoate.

Workup

  1. extractionthe aqueous was extracted with DCM
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe resulting residue was purified by flash chromatography (12 g column)
  5. washeluting with 10 to 30% EtOAc/heptane

Sources & evidence

ORD record
ord-c4409e2e86494cd9a2c210da795e9bb2
Source dataset
uspto-grants-2014_12
Patent number
US08912227B1

Reaction notes

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