Bromoacetone → 2-Methylindolizine-6-carbonitrile

HRID 216668

反応式

HRID 216668 の反応式
Br[CH2:2][C:3](=O)[CH3:4].[C:6]([C:8]1[CH:9]=[CH:10][C:11]([CH3:14])=[N:12][CH:13]=1)#[N:7]>S1(CCCC1)(=O)=O.CCOC(C)=O>[CH3:4][C:3]1[CH:14]=[C:11]2[N:12]([CH:2]=1)[CH:13]=[C:8]([C:6]#[N:7])[CH:9]=[CH:10]2

参加物

5

反応物 2

HCID 11715BromoacetoneHCID 2819956-Methylpyridine-3-carbonitrile

生成物 1

HCID 5933682-Methylindolizine-6-carbonitrile収率 84%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 31347Sulfolane溶媒

反応条件

温度
45 °C

実験手順

1-Bromo-propan-2-one (2.26 ml) is added under an atmosphere of argon to a solution of 5-cyano-2-methylpyridine (5.0 g, 41.9 mmol) in sulfolane (30 ml). The reaction mixture is stirred for 48 hours at 45° C., then diluted with EtOAc. The precipitated salt is filtered off and dissolved in water (50 ml). The aqueous solution is washed with EtOAc, then a 10% aqueous solution of NaHCO3 (30 ml) is added, and the mixture is heated to reflux for 1 hour. After cooling, the reaction mixture is filtered, and the filtrate is extracted three times with EtOAc. The combined organic layers are dried over Na2SO4, filtered, and concentrated in vacuo. The residue is purified via flash chromatography (hexane/EtOAc 8:1, +0.2% NEt3) to afford the title compound (5.50 g, 84%). 1H NMR (400 MHz, d6-DMSO): δ=9.10-9.09 (m, 1H), 7.59 (s, 1H), 7.55 (d, J=9.0 Hz, 1H), 6.90 (dd, J=9.3/1.7 Hz, 1H), 6.55 (s, 1H) 2.39 (s, 3H). MS (ES+): 157 (M+H)+.

後処理

  1. filtrationThe precipitated salt is filtered off
  2. dissolutiondissolved in water (50 ml)
  3. washThe aqueous solution is washed with EtOAc
  4. additiona 10% aqueous solution of NaHCO3 (30 ml) is added
  5. temperaturethe mixture is heated
  6. temperatureto reflux for 1 hour
  7. temperatureAfter cooling
  8. filtrationthe reaction mixture is filtered
  9. extractionthe filtrate is extracted three times with EtOAc
  10. dry with materialThe combined organic layers are dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue is purified via flash chromatography (hexane/EtOAc 8:1, +0.2% NEt3)

出典と根拠

ORDレコード
ord-a6f92e900021461a8118fd1047605029
出典データセット
uspto-grants-2012_06
特許番号
US08193236B2

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