Sodium hydride → 5-chloro-1-[(2-fluoropyridin-3-yl)methyl]-1H-indole

HRID 1896376ノート

反応式

HRID 1896376 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[Na+].Cl[CH2:14][C:15]1[C:16]([F:21])=[N:17][CH:18]=[CH:19][CH:20]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:14][C:15]1[C:16]([F:21])=[N:17][CH:18]=[CH:19][CH:20]=1)[CH:6]=[CH:5]2

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 871105-ChloroindoleHCID 226413043-(Chloromethyl)-2-fluoropyridine

生成物 1

HCID 577430625-chloro-1-[(2-fluoropyridin-3-yl)methyl]-1H-indole収率 59%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

In a 50 ml, three-necked flask fitted with a magnetic stirrer under inert atmosphere, 5-chloro-1H-indole x70 (1.13 g, 7.43 mmol) is dissolved in dry DMF (20 ml). At 0° C., NaH (327 mg, 8.18 mmol, 60% in mineral oil) is added and the mixture is stirred at this temperature for 0.3 h. A solution of 3-(chloromethyl)-2-fluoropyridine x71 (obtained from (2-fluoropyridin-3-yl)methanol and SOCl2 (1.3 g, 8.92 mmol)) in DMF (5 ml) is then added and stirring is continued for 0.5 h at 0° C. The reaction mixture is poured on ice and the aqueous phase is extracted three times with AcOEt. The combined organic phases are dried over MgSO4, filtered and concentrated. Purification by chromatography on silicagel (Hexane/AcOEt: 9/1 (v/v)) affords 5-chloro-1-[(2-fluoropyridin-3-yl)methyl]-1H-indole x72 as a solid (1.13 g).

後処理

  1. stirringstirring
  2. waitis continued for 0.5 h at 0° C
  3. additionThe reaction mixture is poured on ice
  4. extractionthe aqueous phase is extracted three times with AcOEt
  5. dry with materialThe combined organic phases are dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by chromatography on silicagel (Hexane/AcOEt: 9/1 (v/v))

出典と根拠

ORDレコード
ord-9d5dc4d249424b848e0749d8cf9dd915
出典データセット
uspto-grants-2013_08
特許番号
US08518943B2

反応ノート

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