2,2'-Bipyridine → methyl 6-bromo-1-cyclopropyl-1H-indole-4-carboxylate

HRID 42511

반응식

HRID 42511 반응식
[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][NH:8][C:9]=2[CH:10]=1.[CH:15]1(B(O)O)[CH2:17][CH2:16]1.C(=O)([O-])[O-].[Na+].[Na+].N1C=CC=CC=1C1C=CC=CN=1.[NH4+].[Cl-]>ClCCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][N:8]([CH:15]3[CH2:17][CH2:16]3)[C:9]=2[CH:10]=1

참가 물질

10

반응물 5

HCID 14742,2'-BipyridineHCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 2760897Cyclopropylboronic acidHCID 13770009methyl 6-bromo-1H-indole-4-carboxylate

생성물 1

HCID 67467490methyl 6-bromo-1-cyclopropyl-1H-indole-4-carboxylate수율 71.7%

시약·촉매·용매 4

HCID 8895Cupric acetate촉매HCID 111,2-Dichloroethane용매2회HCID 962Water용매HCID 8857Ethyl Acetate용매

반응 조건

온도
70 °C

실험 절차

In a oven dried 100 ml RBF equipped, stir bar, septum and Nitrogen inlet was added methyl 6-bromo-1H-indole-4-carboxylate (0.508 g, 2.0 mmol) and 1,2-dichloroethane (7 mL). The solution was stirred for 15 min, then cyclopropylboronic acid (0.344 g, 4.00 mmol) and sodium carbonate (0.424 g, 4.00 mmol) were added. Diluted copper(II) acetate (0.363 g, 2.000 mmol) and 2,2′-bipyridine (0.312 g, 2.000 mmol) in 1,2-dichloroethane (12 mL), heated the mixture, and added the hot suspension to the reaction. The reaction was heated at 70° C. and monitored by LCMS. Stopped heating after 6 h and allowed to sit for 3 days at RT. Added to reaction saturated NH4Cl and water. Extracted with DCM (2×). The combined organics were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification of the residue by column chromatography (24 g Isco silica column; gradient B: 3-25%. A:hexane. B: ethyl acetate) to give methyl 6-bromo-1-cyclopropyl-1H-indole-4-carboxylate (0.43 g, 1.433 mmol, 71.6% yield) as a yellow residue.

후처리

  1. customIn a oven dried 100 ml RBF
  2. customequipped
  3. stirringThe solution was stirred for 15 min
  4. additionadded the hot suspension
  5. customto the reaction
  6. temperatureStopped heating after 6 h
  7. extractionExtracted with DCM (2×)
  8. washThe combined organics were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification of the residue by column chromatography (24 g Isco silica column

출처 및 근거

ORD 기록
ord-99ae45ff81a148048b4dca26373011f4
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536179B2

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