Potassium Carbonate → Methyl 5-(4-(1,1-difluoroethyl)phenyl)nicotinate

HRID 661244노트

반응식

HRID 661244 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[CH3:9])=[CH:4][CH:3]=1.Cl.[CH3:13][O:14][C:15]([C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[N:21][CH:22]=1)=[O:16].C(=O)([O-])[O-].[K+].[K+].[F-].[K+]>C1(C)C=CC=CC=1.C(O)C.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:10][C:8]([C:5]1[CH:6]=[CH:7][C:2]([C:19]2[CH:20]=[N:21][CH:22]=[C:17]([CH:18]=2)[C:15]([O:14][CH3:13])=[O:16])=[CH:3][CH:4]=1)([F:11])[CH3:9]

참가 물질

10

반응물 4

HCID 11430Potassium CarbonateHCID 522689Potassium FluorideHCID 451588471-Bromo-4-(1,1-difluoroethyl)benzeneHCID 66890177[5-(Methoxycarbonyl)pyridin-3-yl]boronic acid hydrochloride

생성물 1

HCID 58116582Methyl 5-(4-(1,1-difluoroethyl)phenyl)nicotinate

시약·촉매·용매 5

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 962Water용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of 2.98 g (13.3 mmol) of the compound from Example 68A in toluene (25.0 ml) was admixed under argon at RT with 3.62 g (16.7 mmol) of the compound from Example 29A in ethanol (8.4 ml) and 2.03 g (14.7 mmol) of potassium carbonate. After stirring for 10 min, 1.54 g (1.34 mmol) of tetrakis(triphenylphosphine)palladium and then 2.33 g (40.0 mmol) of potassium fluoride in water (5.8 ml) were added. The mixture was stirred under reflux for 8 h, and the reaction solution was cooled and diluted with ethyl acetate. The reaction solution was washed in water, and the organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. The residue was purified by means of column chromatography (silica gel, dichloromethane/methanol 100:1→80:1). Yield: 2.62 g (69% of theory, 4:1 mixture of methyl and ethyl ester)

후처리

  1. stirringThe mixture was stirred
  2. temperatureunder reflux for 8 h
  3. temperaturethe reaction solution was cooled
  4. washThe reaction solution was washed in water
  5. dry with materialthe organic phase was dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by means of column chromatography (silica gel, dichloromethane/methanol 100:1→80:1)
  9. additionYield: 2.62 g (69% of theory, 4:1 mixture of methyl and ethyl ester)

출처 및 근거

ORD 기록
ord-a40fb95621dc4a9abb0abe87f4a2482c
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084469B2

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