Tris(1,1-dimethylethyl)phosphine → 5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile

HRID 1591834Notes

Reaction equation

HRID 1591834 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([O:9][C:10]([F:13])([F:12])[F:11])[CH:3]=1.[C:14]([C:16]1[N:20]([CH3:21])[C:19](B(O)O)=[CH:18][CH:17]=1)#[N:15].[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>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]>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([C:19]2[N:20]([CH3:21])[C:16]([C:14]#[N:15])=[CH:17][CH:18]=2)=[CH:3][C:4]=1[O:9][C:10]([F:13])([F:12])[F:11]

Participants

6

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 7373824-Bromo-2-(trifluoromethoxy)anilineHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acid

Product 1

HCID 160505285-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrileYield 71.1%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

4-Bromo-2-(trifluoromethoxy)aniline (1.3 g, 5.0 mmol), 5-cyano-1-methyl-1H-pyrrol-2-yl boronic acid (0.9 g, 6.0 mmol), potassium fluoride (0.96 g, 16.5 mmol), and tris(dibenzylideneacetone)dipalladium (0.12 g, 0.12 mmol) were placed in an oven dried flask under nitrogen and THF (12.5 mL) was added. Tri-t-butylphosphine (10 wt % in hexane) (0.356 mL, 0.24 mol) was added and the reaction was stirred for 16 hours. The reaction mixture was filtered through silica, rinsed with ethyl acetate, and concentrated. The crude product was pre-adsorbed onto the Celite™ reagent and purified via Isco chromatography (the Redisep® column, silica, gradient 5-30% ethyl acetate in hexane) to afford 1.0 g (71%) of 5-[4-amino-3-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile.

Workup

  1. customdried flask under nitrogen
  2. additionTHF (12.5 mL) was added
  3. filtrationThe reaction mixture was filtered through silica
  4. washrinsed with ethyl acetate
  5. concentrationconcentrated
  6. custompurified via Isco chromatography (the Redisep® column, silica, gradient 5-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ea220ee8fa194283bd03f23705775c9e
Source dataset
uspto-grants-2007_11
Patent number
US07291643B2

Reaction notes

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