Potassium Carbonate → HCID 21964293、化合物

HRID 2373484ノート

反応式

HRID 2373484 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH2:11][OH:12])=[CH:5]2.[CH3:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].BrC1C=C2C(=CC=1)N(CC1C=CC(C(C)(C)C)=CC=1)C=C2>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:13][C:14]1[CH:19]=[C:18]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6]([CH2:11][OH:12])=[CH:5]3)[CH:17]=[CH:16][CH:15]=1

参加物

9

反応物 4

HCID 11430Potassium CarbonateHCID 27339503-Tolylboronic acid2 回HCID 13567955(5-Bromo-1H-indol-2-yl)methanolHCID 21964287HCID 21964287、化合物

生成物 1

HCID 21964293HCID 21964293、化合物収率 63.5%

試薬・触媒・溶媒 4

HCID 74236Tetrabutylammonium Bromide触媒HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
70 °C

実験手順

A mixture of (5-bromo-1H-indol-2-yl) methanol (9 g, 39.8 mmol), 3-methylbenzeneboronic acid (6.14 g, 43.78 mmol), potassium carbonate (13.75 g, 99.5 mmol), palladium(II) acetate (0.045 g) and tetrabutylammonium bromide (12.84 g, 39.8 mmol) in 10% dioxane in water (degassed, 0.38 L) was stirred at 70° C. The reaction was monitored by TLC. Additional 3-methylbenzeneboronic acid (5.6 g, 39.8 mmol) was added. After no 5-bromo-1-(4-tert-butylbenzyl)-1H-indole was detected by TLC, the reaction was cooled to room temperature and the solvent was decanted. The residual thick oil was stirred with hexane. The hexane was decanted and the residue was partitioned between water and ethyl acetate. The ethyl acetate layer was separated, washed with water filtered and concentrated. The residue was purified by flash column chromatography using hexane/ethyl acetate (55:45) as an eluant to give [5-(3-Methylphenyl)-1H-indol-2-yl]methanol as a brown solid (6.0 g). Reaction of [5-(3-Methylphenyl)-1H-indol-2-yl]methanol with acetyl chloride according to the procedure described in step 4 of Example 1 afforded the title compound as an oil (3.94 g); Mass spectrum (ESI, [M−H]−) m/z 278. 1H NMR (400 MHz, DMSO-d6) δ 7.76 (s, 1H), 7.46 (s, 1H), 7.42-7.36 (m, 3H), 7.30 (s, 1H), 7.10 (d, 1H, J=7.48 Hz), 6.50 (s, 1H), 2.37 (s, 3H), and 2.07 ppm (s, 3H).

後処理

  1. temperaturethe reaction was cooled to room temperature
  2. customthe solvent was decanted
  3. stirringThe residual thick oil was stirred with hexane
  4. customThe hexane was decanted
  5. customthe residue was partitioned between water and ethyl acetate
  6. customThe ethyl acetate layer was separated
  7. washwashed with water
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash column chromatography

出典と根拠

ORDレコード
ord-4c3876b9a12e41d58fd83badd8708aa8
出典データセット
uspto-grants-2008_12
特許番号
US07459478B2

反応ノート

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