Sodium hydride → 2-(5,6-dihydro-2H-4-pyranyl)-1-(4-fluorobenzyl)-5-methanesulfonyl-indole

HRID 1814085Notes

Reaction equation

HRID 1814085 reaction equation
[O:1]1[CH2:6][CH2:5][C:4]([C:7]2[NH:8][C:9]3[C:14]([CH:15]=2)=[CH:13][C:12]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:11][CH:10]=3)=[CH:3][CH2:2]1.[H-].[Na+].[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Br)=[CH:25][CH:24]=1.[Cl-].[NH4+]>CN(C)C=O>[O:1]1[CH2:6][CH2:5][C:4]([C:7]2[N:8]([CH2:27][C:26]3[CH:29]=[CH:30][C:23]([F:22])=[CH:24][CH:25]=3)[C:9]3[C:14]([CH:15]=2)=[CH:13][C:12]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:11][CH:10]=3)=[CH:3][CH2:2]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 680214-Fluorobenzyl bromideHCID 225043862-(5,6-dihydro-2H-4-pyranyl)-5-methanesulfonylindole

Product 1

HCID 98215002-(5,6-dihydro-2H-4-pyranyl)-1-(4-fluorobenzyl)-5-methanesulfonyl-indoleYield 80.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound obtained in Example 14 (4) (16.5 mg) in N,N-dimethylformamide (3 ml), 60% sodium hydride (3.6 mg) was added under nitrogen atmosphere at 0° C. and the mixture was stirred for 30 minutes, followed by additin of 4-fluorobenzyl bromide (22.7 mg), and the mixture was stirred at 15 to 30° C. for 15 hours. The reaction solution was then poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous NaCl solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was separated using silica gel preparative thin-layer chromatography (hexane:ethyl acetate=1:1) to obtain 18.4 mg of the desired product as a white powder.

Workup

  1. stirringthe mixture was stirred at 15 to 30° C. for 15 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materiala saturated aqueous NaCl solution, dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was separated

Sources & evidence

ORD record
ord-f36467c39ac447c395b7068910b7bccf
Source dataset
uspto-grants-2005_04
Patent number
US06875770B2

Reaction notes

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