Water → 4-((4-Fluoro-1-methylpiperidin-4-yl)methoxy)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 2040224Notes

Reaction equation

HRID 2040224 reaction equation
[F:1][C:2]1([CH2:9][OH:10])[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[H-].[Na+].F[C:14]1[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][C:15]=1[S:24]([C:27]([F:30])([F:29])[F:28])(=[O:26])=[O:25].O>O1CCCC1.ClCCl>[F:1][C:2]1([CH2:9][O:10][C:14]2[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][C:15]=2[S:24]([C:27]([F:28])([F:30])[F:29])(=[O:26])=[O:25])[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 962Water2×HCID 24758Sodium hydrideHCID 24729611(4-Fluoro-1-methylpiperidin-4-yl)methanolHCID 250584524-Fluoro-3-((trifluoromethyl)sulfonyl)benzenesulfonamide

Product 1

HCID 671267294-((4-Fluoro-1-methylpiperidin-4-yl)methoxy)-3-(trifluoromethylsulfonyl)benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of (4-fluoro-1-methylpiperidin-4-yl)methanol (0.315 g) in tetrahydrofuran (5 mL) was added sodium hydride (0.342 g). After stirring for 15 minutes, 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide (0.658 g) was added as a solution in tetrahydrofuran (2 mL) followed by additional tetrahydrofuran (5 mL). After stirring for 1 hour, the reaction was poured in dichloromethane (50 mL) and water (25 mL) and the pH of the water layer was adjusted to 8. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The resulting oil was chromatographed over silica gel (Reveleris 40 g) eluting with a gradient of 1.0% to 10% 7N NH3 in methanol/dichloromethane over 20 minutes then maintaining 10% 7N NH3 in methanol/dichloromethane for 5 minutes (flow=30 mL/min) to provide the title compound.

Workup

  1. stirringAfter stirring for 1 hour
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting oil was chromatographed over silica gel (Reveleris 40 g)
  6. washeluting with a gradient of 1.0% to 10% 7N NH3 in methanol/dichloromethane over 20 minutes
  7. temperaturethen maintaining 10% 7N NH3 in methanol/dichloromethane for 5 minutes (flow=30 mL/min)

Sources & evidence

ORD record
ord-05d90cbdab4c49eea6dea4fd3cc8d69a
Source dataset
uspto-grants-2013_11
Patent number
US08580794B2

Reaction notes

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