Hydrochloric Acid → 4-[(3,4-dichlorobenzyl)oxy]-N-[(dimethylamino)sulfonyl]benzamide

HRID 1525651Notes

Reaction equation

HRID 1525651 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5][OH:6].[H-].[Na+].[CH3:13][N:14]([CH3:28])[S:15]([NH:18][C:19](=[O:27])[C:20]1[CH:25]=[CH:24][C:23](F)=[CH:22][CH:21]=1)(=[O:17])=[O:16].Cl>C1COCC1.CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5][O:6][C:23]1[CH:24]=[CH:25][C:20]([C:19]([NH:18][S:15]([N:14]([CH3:28])[CH3:13])(=[O:17])=[O:16])=[O:27])=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 157283,4-Dichlorobenzyl alcoholHCID 24758Sodium hydrideHCID 47363087N-[(dimethylamino)sulfonyl]-4-fluorobenzamide

Product 1

HCID 716161484-[(3,4-dichlorobenzyl)oxy]-N-[(dimethylamino)sulfonyl]benzamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,4-dichlorobenzyl alcohol (500 mg, 2.8 mmol) in THF (20 mL) was added sodium hydride (113 mg, 2.8 mmol, 60% dispersion in mineral oil) and stirred at room temperature for 2 hours and then at 50° C. for 30 minutes. Cooled to room temperature and the solvent removed in vacuo to afford an orange solid. This was dissolved in DMSO (5 mL) to which was added a solution of N-[(dimethylamino)sulfonyl]-4-fluorobenzamide (Preparation 11, 580 mg, 2.3 mmol) in DMSO (10 mL) slowly. The dark red solution was heated at 50° C. for 18 h then 120° C. for 2 hours. The mixture was cooled and poured onto water (50 mL) containing 2M HCl (30 mL) and extracted with EtOAc (2×30 mL), washed with 1M HCl (30 mL) and dried over MgSO4, filtered and solvent removed in vacuo to give 1.9 g of crude residue that was purified using reverse phase preparative HPLC to afford the title compound.

Workup

  1. waitat 50° C. for 30 minutes
  2. temperatureCooled to room temperature
  3. customthe solvent removed in vacuo
  4. customto afford an orange solid
  5. temperatureThe dark red solution was heated at 50° C. for 18 h
  6. wait120° C. for 2 hours
  7. temperatureThe mixture was cooled
  8. additionpoured onto water (50 mL)
  9. extractionextracted with EtOAc (2×30 mL)
  10. washwashed with 1M HCl (30 mL)
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customsolvent removed in vacuo
  14. customto give 1.9 g of crude residue that
  15. customwas purified

Sources & evidence

ORD record
ord-e73def409fe74446b26257206096b016
Source dataset
uspto-grants-2015_07
Patent number
US09085517B2

Reaction notes

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