Sodium hydride → N-(2,4-dimethylphenyl)-N-isobutyl-4-(((tetrahydro-2H-pyran-4-yl)methoxy)methyl)benzenesulfonamide

HRID 1487053Notes

Reaction equation

HRID 1487053 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=2[CH3:24])[CH2:13][CH:14]([CH3:16])[CH3:15])(=[O:11])=[O:10])=[CH:5][CH:4]=1.[O:25]1[CH2:30][CH2:29][CH:28]([CH2:31][OH:32])[CH2:27][CH2:26]1.[H-].[Na+]>CC1CCCO1.CS(C)=O.ClCCl.O>[CH3:24][C:18]1[CH:19]=[C:20]([CH3:23])[CH:21]=[CH:22][C:17]=1[N:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[S:9]([C:6]1[CH:5]=[CH:4][C:3]([CH2:2][O:32][CH2:31][CH:28]2[CH2:29][CH2:30][O:25][CH2:26][CH2:27]2)=[CH:8][CH:7]=1)(=[O:10])=[O:11]

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 2773573(Oxan-4-yl)methanolHCID 867315854-(bromomethyl)-N-(2,4-dimethylphenyl)-N-isobutylbenzenesulfonamide

Product 1

HCID 72190215N-(2,4-dimethylphenyl)-N-isobutyl-4-(((tetrahydro-2H-pyran-4-yl)methoxy)methyl)benzenesulfonamide

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of crude 4-(bromomethyl)-N-(2,4-dimethylphenyl)-N-isobutylbenzenesulfonamide (100 mg, 0.122 mmol) and (tetrahydro-2H-pyran-4-yl)methanol (14.15 mg, 0.122 mmol) in 2-methyltetrahydrofuran (2-MeTHF) (1 mL) and dimethyl sulfoxide (DMSO) (0.5 mL) was added sodium hydride (approximately 4.87 mg, 0.122 mmol, 60% dispersed in oil) in one charge. The reaction mixture was stirred at 20° C. for 16 hours. The reaction was then quenched with methanol (0.5 mL) and water (0.5 mL) and concentrated in vacuo to give a residue in DMSO. This was diluted with dichloromethane (10 mL) and water (10 mL) and stirred vigorously for 10 minutes. The layers were separated by hydrophobic frit and the organic fraction evaporated to give the crude product. The sample was then purified by mass directed autoprep (formic acid modifier). The appropriate fractions were concentrated under a stream of nitrogen to give the required product, 4.2 mg. LCMS [LCMS1] Rt 1.44 min, m/z (ES+) 446 (M+H).

Workup

  1. additioncharge
  2. customThe reaction was then quenched with methanol (0.5 mL) and water (0.5 mL)
  3. concentrationconcentrated in vacuo
  4. customto give a residue in DMSO
  5. stirringstirred vigorously for 10 minutes
  6. customThe layers were separated by hydrophobic frit
  7. customthe organic fraction evaporated
  8. customto give the crude product
  9. customThe sample was then purified by mass
  10. concentrationThe appropriate fractions were concentrated under a stream of nitrogen

Sources & evidence

ORD record
ord-9506c3f27c74452791882c3d7d25c153
Source dataset
uspto-grants-2016_08
Patent number
US09428452B2

Reaction notes

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