Sodium hydride → N-[1-(4-Bromo-phenyl)-cyclopropanecarbonyl]-methanesulfonamide

HRID 631928Notes

Reaction equation

HRID 631928 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[H-].[Na+].[CH3:22][S:23]([NH2:26])(=[O:25])=[O:24]>CN(C=O)C.C(Cl)Cl.Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([NH:26][S:23]([CH3:22])(=[O:25])=[O:24])=[O:13])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 72879MethanesulfonamideHCID 162279661-(4-Bromophenyl)cyclopropane-1-carboxylic acid

Product 1

HCID 66577406N-[1-(4-Bromo-phenyl)-cyclopropanecarbonyl]-methanesulfonamideYield 51.9%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent3×HCID 6344DichloromethaneSolvent2×

Procedure

In a 100 ml, round-bottomed flask, 1-(4-bromo-phenyl)-cyclopropanecarboxylic acid (4 g, 16.6 mmol) was combined with DCM (15 mL) and 3 drops of DMF to give a white suspension. To this was added drop wise a clear solution of oxalyl chloride (6.96 g, 4.8 mL, 54.8 mmol) dissolved in DCM (6 mL). After 10 min, the mixture became clear and the reaction was stirred at room temperature for 2 hr. The reaction was concentrated, dried from toluene and hexanes, and stored in a freezer overnight. In a 200 mL round-bottomed flask, NaH (60% mineral dispersion, 876 mg, 36.5 mmol) was washed with hexanes and the resulting solid was diluted with DMF (6 mL) to give a white suspension. The suspension was cooled in an ice bath and methanesulfonamide (3.16 g, 33.2 mmol) dissolved in DMF (6 mL) was added drop wise under nitrogen. After addition (5 min) the ice bath was removed and the reaction was warmed to room temperature overnight. The reaction was cooled in an ice bath, the acid chloride previously prepared and dissolved in DMF (6 mL) was added drop wise, and the reaction was warmed to room temperature overnight. The reaction was diluted with 0.2 N HCl (200 mL) and extracted with EtOAc (2×100 mL). The organic layers were washed with brine, combined, dried over MgSO4, and concentrated. The crude material was dissolved in minimal DCM and purified by flash chromatography (silica gel, 0% to 60% EtOAc in hexanes, 0.5% AcOH). The appropriate fractions were combined, concentrated, and dried from DCM/hexanes yielding N-[1-(4-bromo-phenyl)-cyclopropanecarbonyl]-methanesulfonamide (2.74 g, 51.9% yield) as a white solid. LC/MS calcd. for C11H12BrNO3S (m/e) 317/319, obsd. 318/320 (M+H, ES+).

Workup

  1. customto give a white suspension
  2. concentrationThe reaction was concentrated
  3. dry with materialdried from toluene and hexanes
  4. waitstored in a freezer overnight
  5. customto give a white suspension
  6. temperatureThe suspension was cooled in an ice bath
  7. additionwas added drop wise under nitrogen
  8. customwas removed
  9. temperaturethe reaction was warmed to room temperature overnight
  10. temperatureThe reaction was cooled in an ice bath
  11. customthe acid chloride previously prepared
  12. additionwas added drop wise
  13. temperaturethe reaction was warmed to room temperature overnight
  14. extractionextracted with EtOAc (2×100 mL)
  15. washThe organic layers were washed with brine
  16. dry with materialdried over MgSO4
  17. concentrationconcentrated
  18. dissolutionThe crude material was dissolved in minimal DCM
  19. custompurified by flash chromatography (silica gel, 0% to 60% EtOAc in hexanes, 0.5% AcOH)
  20. concentrationconcentrated
  21. dry with materialdried from DCM/hexanes

Sources & evidence

ORD record
ord-0b9161b0158d47dfbd84381844ca144c
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

Loading…