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

HRID 62410

反応式

HRID 62410 の反応式
[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

参加物

10

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 8895Cupric acetate触媒HCID 111,2-Dichloroethane溶媒2 回HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

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. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.96-1.01 (m, 2H) 1.06-1.12 (m, 2H) 3.52 (dt, J=7.20, 3.47 Hz, 1H) 3.90 (s, 3H) 6.85-6.91 (m, 1H) 7.57 (d, J=3.03 Hz, 1H) 7.82 (d, J=1.77 Hz, 1H) 8.04 (d, J=1.01 Hz, 1H). MS(ES) [M+H]+ 294.1.

後処理

  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

出典と根拠

ORDレコード
ord-c0ef96da48e94c549e4dab545f4231b9
出典データセット
uspto-grants-2016_09
特許番号
US09446041B2

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