Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → Benzamide

HRID 1264344Notes

Reaction equation

HRID 1264344 reaction equation
O.ON1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2N=N1.[NH2:12]OC1CCCCO1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)C[C:21]2=[O:22]>CN(C=O)C>[C:21]([NH2:12])(=[O:22])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 27960291-Hydroxybenzotriazole hydrateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamine

Product 1

HCID 2331BenzamideYield 388.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[4-benzo[b]thiophene-2-sulfonylamino]benzoic acid (300 mg, 0.90 mmol) in DMF (20 mL) at room temperature were added 1-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 207 mg, 1.08 mmol), and 1-Hydroxybenzotriazole hydrate (HOBT, 182 mg, 1.35 mmol). The mixture was stirred 20 min. at room temperature then NH2OTHP (158 mg, 1.35 mmol) was added. The resulting mixture was heated at 50° C. for 24 h then stirred at room temperature for 24 h. The DMF solvent was evaporated under reduced pressure and the residue was dissolved in CH2Cl2 and washed with brine or a saturated aqueous solution of NaHCO3. The combined organic extracts were dried over (MgSO4) then condensed. The crude compound was purified by flash chromatography using CH2Cl2/MeOH (9:1) as solvent mixture. The residue was then dissolved in methanol (20 mL) then 10-camphorsulfonic acid (CSA, 100 mg, 0.45 mmol) was added. The mixture was stirred 2 h at room temperature then the solvents were evaporated under reduced pressure at room temperature to avoid thermal decomposition. The crude was purified by flash chromatography using CH2Cl2/MeOH (9:1) as solvent mixture. A second purification was performed using a preparative high pressure liquid chromatography using a gradient of water/CH3CN (10-85%) as solvent giving the title compound 13 as a red solid (212 mg, 68%).

Workup

  1. temperatureThe resulting mixture was heated at 50° C. for 24 h
  2. stirringthen stirred at room temperature for 24 h
  3. customThe DMF solvent was evaporated under reduced pressure
  4. dissolutionthe residue was dissolved in CH2Cl2
  5. washwashed with brine
  6. dry with materialThe combined organic extracts were dried over (MgSO4)
  7. customcondensed
  8. customThe crude compound was purified by flash chromatography
  9. dissolutionThe residue was then dissolved in methanol (20 mL)
  10. stirringThe mixture was stirred 2 h at room temperature
  11. customthe solvents were evaporated under reduced pressure at room temperature
  12. customThe crude was purified by flash chromatography
  13. customA second purification

Sources & evidence

ORD record
ord-d310129b4ae642928bf8db26900e6782
Source dataset
uspto-grants-2003_04
Patent number
US06541661B1

Reaction notes

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