Sodium hydride → N-(4-Fluoro-phenyl)-N-isobutyl-4-(1-methanesulfonyl-piperidin-4-yloxy)-benzenesulfonamide

HRID 1049010Notes

Reaction equation

HRID 1049010 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]1)(=[O:4])=[O:3].[H-].[Na+].F[C:15]1[CH:20]=[CH:19][C:18]([S:21]([N:24]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[CH2:25][CH:26]([CH3:28])[CH3:27])(=[O:23])=[O:22])=[CH:17][CH:16]=1>O>[F:35][C:32]1[CH:31]=[CH:30][C:29]([N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[S:21]([C:18]2[CH:19]=[CH:20][C:15]([O:11][CH:8]3[CH2:7][CH2:6][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:10][CH2:9]3)=[CH:16][CH:17]=2)(=[O:23])=[O:22])=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 222729811-Methanesulfonylpiperidin-4-olHCID 86721868HCID 86721868, compound

Product 1

HCID 76284182N-(4-Fluoro-phenyl)-N-isobutyl-4-(1-methanesulfonyl-piperidin-4-yloxy)-benzenesulfonamideYield 34.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 1-methanesulfonyl-piperidin-4-ol (61 mg) in anhydrous tetrohydrofuran (5 mL) at room temperature was added NaH (60% dispersion in mineral oil, 15 mg, 369 μmol) and the reaction was stirred at room temperature for 30 minutes. 4-Fluoro-N-(4-fluoro-phenyl)-N-isobutyl-benzenesulfonamide (100 mg, 308 μmol) was added and the reaction was heated at 90° C. for 3 hours. The reaction was allowed to cool to room temperature, water was added and then extracted with EtOAc, concentrated, purified by preparative reverse-phase HPLC and then freeze dried to give the title compound (51.8 mg). 1H NMR (400 MHz, DMSO): δ 7.44 (d, J=8.8 Hz, 2H), 7.13-7.14 (m, 7H), 4.69 (t, J=3.8 Hz, 1H), 3.35 (d, J=10.8 Hz, 4H), 3.28 (d, J=7.4 Hz, 3H), 3.12-3.14 (m, 2H), 2.91 (s, 3H), 2.03 (br s, 3H), 1.71-1.79 (m, 3H), 1.41 (t, J=6.8 Hz, 1H), 0.84 (d, J=6.6 Hz, 6H). LCMS (m/z, Method B) ES+ 484.9 [M+1]+.

Workup

  1. temperaturethe reaction was heated at 90° C. for 3 hours
  2. temperatureto cool to room temperature
  3. extractionextracted with EtOAc
  4. concentrationconcentrated
  5. custompurified by preparative reverse-phase HPLC
  6. customfreeze dried

Sources & evidence

ORD record
ord-5690b11ab1a940fead1bd1803bd20f12
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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