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

HRID 220042노트

반응식

HRID 220042 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 48A in toluene (25.0 ml) was admixed under argon at RT with 3.62 g (16.7 mmol) of the compound from Example 33A 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-6a36d0dad148411fad4263377068b6fe
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202862B2

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