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

HRID 1924239Notes

Reaction equation

HRID 1924239 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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).

Workup

  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))

Sources & evidence

ORD record
ord-60b3d30d3820459bb57dfbea3c1f2008
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

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