2-Bromopyridine → Methyl 1-cyclopentyl-3-methyl-2-(2-pyridyl)indole-5-carboxylate

HRID 1174639

반응식

HRID 1174639 반응식
Br[C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.COB([O:16][CH3:17])OC.[C:18]1([CH3:25])[CH:23]=[CH:22][C:21](P)=CC=1.Br[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1.[C:33](=[O:36])([O-])[O-].[K+].[K+].[CH2:39]1COCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CC(OC)(C)C.CO>[CH:21]1([N:3]2[C:4]3[C:9](=[CH:8][C:7]([C:33]([O:16][CH3:17])=[O:36])=[CH:6][CH:5]=3)[C:10]([CH3:39])=[C:2]2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)[CH2:22][CH2:23][CH2:18][CH2:25]1

참가 물질

11

반응물 6

HCID 79732-BromopyridineHCID 8028Tetrahydrofuran2회HCID 8470Trimethyl borateHCID 11430Potassium CarbonateHCID 43799374-TolylphosphineHCID 118056312-bromo-1H-indole

생성물 1

HCID 21974266Methyl 1-cyclopentyl-3-methyl-2-(2-pyridyl)indole-5-carboxylate

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 887Methanol용매HCID 962Water용매HCID 15413tert-Butyl methyl ether용매

반응 조건

온도
-78 °C

실험 절차

The 2-bromoindole from above (1.53 g, 4.55 mmol, 1.0 equiv.) was dissolved in anhydrous THF (20 mL) and the solution was cooled to −78° C. under an argon atmosphere. N-BuLi (solution in hexane, 4.78 mmol, 1.05 equiv.) was added dropwise and the mixture was stirred 30 min in the cold. Trimethylborate (0.62 mL, 5.46 mmol, 1.2 equiv.) was added dropwise and the solution stirred at −78° C. for 40 min and then at 0° C. for 1 h. Finally the reaction mixture was allowed to warm up to room temperature and additional THF (20 mL) was added. para-Tolylphosphine (0.083 g, 0.27 mmol, 0.06 equiv.) and 2-bromopyridine (0.86 g, 5.46 mmol, 1.2 equiv.) were then added and the solution was degassed by bubbling argon through for 30 min. Palladium acetate (10 mg, 0.046 mmol, 0.01 equiv.), anhydrous potassium carbonate (1.26 g, 9.1 mmol, 2 equiv.) and MeOH (20 mL) were added and the mixture was refluxed overnight under an argon atmosphere. After cooling to RT, TBME (12 mL) and water (12 mL) were added, the organic phase was separated and the aqueous phase extracted with additional TBME (2×25 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated to give a residue that was purified by flash chromatography on silica gel using 5-10% EtOAc in hexane as eluent: 1.21 g (79%).

후처리

  1. stirringthe solution stirred at −78° C. for 40 min
  2. waitat 0° C. for 1 h
  3. temperatureto warm up to room temperature
  4. customthe solution was degassed
  5. customby bubbling argon through for 30 min
  6. temperaturethe mixture was refluxed overnight under an argon atmosphere
  7. temperatureAfter cooling to RT
  8. customthe organic phase was separated
  9. extractionthe aqueous phase extracted with additional TBME (2×25 mL)
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated
  13. customto give a residue that
  14. customwas purified by flash chromatography on silica gel using 5-10% EtOAc in hexane as eluent

출처 및 근거

ORD 기록
ord-1dc8eae914574be3852fe8e62573e3c4
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07838537B2

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