Tetrafluoroboric acid → 4-Chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid

HRID 1848650노트

반응식

HRID 1848650 반응식
[C:1]([C:4]1[C:5]([O:14][CH3:15])=[CH:6][C:7]([Cl:13])=[C:8](B(O)O)[CH:9]=1)([OH:3])=[O:2].Br[C:17]1[C:22]([C:23]#[N:24])=[CH:21][C:20]([C:25]([F:28])([F:27])[F:26])=[N:19][CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.[H+].[B-](F)(F)(F)F>C(OCC)(=O)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]>[Cl:13][C:7]1[C:8]([C:17]2[CH:18]=[N:19][C:20]([C:25]([F:27])([F:28])[F:26])=[CH:21][C:22]=2[C:23]#[N:24])=[CH:9][C:4]([C:1]([OH:3])=[O:2])=[C:5]([O:14][CH3:15])[CH:6]=1

참가 물질

8

반응물 5

HCID 28118Tetrafluoroboric acidHCID 62657Potassium Phosphate, TribasicHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 441195965-Borono-4-chloro-2-methoxybenzoic acidHCID 569733155-Bromo-2-(trifluoromethyl)isonicotinonitrile

생성물 1

HCID 686021944-Chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid수율 44.4%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매

실험 절차

N2 was bubbled through a solution of THF (8 mL) and water (2 mL) containing 5-carboxy-2-chloro-4-methoxy-phenylboronic acid (460.8 mg, 2.0 mmol) and 5-bromo-2-trifluoromethyl-isonicotinonitrile 1-1 (478 mg, 1.9 mmol) for 10 minutes. K3PO4 (1.2 g, 5.7 mmol), t-Bu3P.HBF4 (82.7 mg, 0.28 mmol), and Pd2 dba3 (91.0 mg, 0.1 mmol) were added under N2 atmosphere. The mixture was sealed, stirred at rt for 3 hrs, and diluted with ethyl acetate. The organic layer was separated, washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified via silica gel flash column chromatography eluting with 10% MeOH in dichloromethane to give 4-chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid (301 mg).

후처리

  1. customN2 was bubbled through a solution of THF (8 mL) and water (2 mL)
  2. customThe mixture was sealed
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified via silica gel flash column chromatography
  9. washeluting with 10% MeOH in dichloromethane

출처 및 근거

ORD 기록
ord-ed5e81890abe45c98dad514d455356b5
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952161B2

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