Sodium Carbonate → 4-Phenyl-1-methyl-indole-3-carboxaldehyde

HRID 2307244노트

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HRID 2307244 반응식
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH:12]=[O:13])=[CH:5][N:6]2[CH3:11].[C:14]1(B(O)O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:14]1([C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[C:4]([CH:12]=[O:13])=[CH:5][N:6]3[CH3:11])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 226053634-Bromo-1-methyl-1H-indole-3-carbaldehyde

생성물 1

HCID 226053884-Phenyl-1-methyl-indole-3-carboxaldehyde

시약·촉매·용매 3

HCID 178419050HCID 178419050, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

To a cold solution (0° C.) of 4-bromo-indole-3-carboxaldehyde (0.767 g, 3.4 mmol) in dry DMF (2 mL) was added NaH (60% dispersion in mineral oil, 173 mg, 4.37 mmol). The resulting mixture was stirred at 0° C. for 20 min. Iodomethane (0.8 mL, excess) was added to the reaction mixture in a drop wise fashion. The cooling bath was removed and the resulting mixture was stirred at room temperature for 1.5 h. The mixture was quenched with water and was extracted repeatedly from EtOAc. The combined organic extracts were washed with water (twice) and brine. After drying over magnesium sulfate, solvent was removed. The resulting solid was taken in hexane and sonicated for 30 min, filtered to provide the product, 4-bromo-1-methyl-indole-3-carboxaldehyde (0.687 g, 85% yield). A mixture of 4-bromo-1-methyl-indole-3-carboxaldehyde (109 mg, 0.45 mmol), phenyl boronic acid (85 mg, 0.69 mmol) in DMF (4 mL) was degassed (argon). To the mixture was added bis(triphenylphosphine)-palladium II chloride (25 mg, 0.035 mmol) followed by addition of 2M Na2CO3 solution (2 mL, 4 mmol) and the mixture was stirred under argon at 100° C. for 18.5 h and then at reflux for 3 h. The mixture was cooled to room temperature. The reaction mixture was diluted with water and extracted repeatedly with ethyl acetate. The combined extract was washed with water (twice) and brine. After drying over anhydrous magnesium sulfate, solvent was removed in vacuo and the crude product was purified by flash chromatography (hexane:EtOAc 1:1). The desired product was isolated as syrup (79% yield). MS: 236, 238.

후처리

  1. customwas degassed (argon)
  2. temperatureat reflux for 3 h
  3. temperatureThe mixture was cooled to room temperature
  4. extractionextracted repeatedly with ethyl acetate
  5. extractionThe combined extract
  6. washwas washed with water (twice) and brine
  7. dry with materialAfter drying over anhydrous magnesium sulfate, solvent
  8. customwas removed in vacuo
  9. customthe crude product was purified by flash chromatography (hexane:EtOAc 1:1)

출처 및 근거

ORD 기록
ord-e241d9383761484090a91dfd43b5d2de
출처 데이터셋
uspto-grants-2004_12
특허 번호
US06831075B2

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