Sodium hydride → 3-Chloro-4-((4-fluoro-1-methylpiperidin-4-yl)methoxy)benzenesulfonamide

HRID 574895Notes

Reaction equation

HRID 574895 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+].[Cl:13][C:14]1[CH:15]=[C:16]([S:21]([NH2:24])(=[O:23])=[O:22])[CH:17]=[CH:18][C:19]=1F>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([S:21]([NH2:24])(=[O:22])=[O:23])[CH:17]=[CH:18][C:19]=1[O:10][CH2:9][C:2]1([F:1])[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 75098833-Chloro-4-fluorobenzenesulfonamideHCID 24729611(4-Fluoro-1-methylpiperidin-4-yl)methanol

Product 1

HCID 671267253-Chloro-4-((4-fluoro-1-methylpiperidin-4-yl)methoxy)benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (4-fluoro-1-methylpiperidin-4-yl)methanol (0.265 g) in tetrahydrofuran (2 mL) was added sodium hydride (0.288 g). After 15 minutes, 3-chloro-4-fluorobenzenesulfonamide (0.377 g) was added as a solution in tetrahydrofuran (1 mL). The reaction was stirred for 2 hours, quenched with water (5 mL), adjusted to pH ˜7 with 1N aqueous HCl, and extracted with dichloromethane (2×25 mL). The organic layer was washed with brine (25 mL), dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (Reveleris 40 g) eluting with a gradient of 0.1% to 10% methanol containing 2N NH3/dichloromethane over 30 minutes gave the title compound.

Workup

  1. customquenched with water (5 mL)
  2. extractionextracted with dichloromethane (2×25 mL)
  3. washThe organic layer was washed with brine (25 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washSilica gel chromatography (Reveleris 40 g) eluting with a gradient of 0.1% to 10% methanol containing 2N NH3/dichloromethane over 30 minutes

Sources & evidence

ORD record
ord-70f4faf328a14d7eac5c07e38e81d29e
Source dataset
uspto-grants-2015_05
Patent number
US09034875B2

Reaction notes

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