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

HRID 1924239노트

반응식

HRID 1924239 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

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).

후처리

  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))

출처 및 근거

ORD 기록
ord-60b3d30d3820459bb57dfbea3c1f2008
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08178533B2

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