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Potassium Phosphate, Tribasic → 2-(2,3-Difluoro-6-methoxy-phenyl)-N-methoxy-N-methyl-isonicotinamide

HRID 1909016
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HRID 1909016 반응식
Br[C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][N:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6].[F:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[C:17]([O:22][CH3:23])[C:16]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[F:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[C:17]([O:22][CH3:23])[C:16]=1[C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][N:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6]
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참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 43727862,3-Difluoro-6-methoxyphenylboronic acidHCID 448186542-Bromo-N-methoxy-N-methylisonicotinamide

생성물 1

HCID 866643432-(2,3-Difluoro-6-methoxy-phenyl)-N-methoxy-N-methyl-isonicotinamide수율 23%

시약·촉매·용매 2

HCID 178418851HCID 178418851, 화합물
촉매
HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

A flask containing 2-bromo-N-methoxy-N-methyl-isonicotinamide (Example 25, using method 2) (3.0 g, 12.2 mmol) 2,3-difluoro-6-methoxyphenylboronic acid (4.6 g, 24.4 mmol)) and 2M aqueous K3PO4 (15 mL, 30.6 mmol) in 1,4-dioxane (40 mL) was successively evacuated and flushed with nitrogen. Pd(PtBu3)2 (268 mg, 0.48 mmol) was then added and the mixture heated at 90° C. for 2 hours. The mixture was cooled, concentrated in vacuo and then partitioned between EtOAc and sat. aqueous NaHCO3 solution. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by SiO2 chromatography (eluting with 30-100% EtOAc/hexane) gave the title compound (0.856 g, 23%). MS(ESI) m/z 309 (M+H)+

후처리

  1. customwas successively evacuated
  2. customflushed with nitrogen
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated in vacuo
  5. custompartitioned between EtOAc and sat. aqueous NaHCO3 solution
  6. washThe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification
  10. washby SiO2 chromatography (eluting with 30-100% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-8eaede80015a49b7976a59d2cffffad1
출처 데이터셋
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08598217B2

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