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

HRID 1591834노트

반응식

HRID 1591834 반응식
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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-ea220ee8fa194283bd03f23705775c9e
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07291643B2

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