Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 3-(4-Benzenesulfonylaminophenyl)-N-hydroxyacrylamide

HRID 2402411Notes

Reaction equation

HRID 2402411 reaction equation
[C:1]1([S:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]=[CH:18][C:19]([OH:21])=O)=[CH:13][CH:12]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.CN(C)CCCN=C=NCC.O.[OH:35][N:36]1C2C=CC=CC=2N=N1.NOC1CCCCO1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>CN(C=O)C>[OH:35][NH:36][C:19](=[O:21])[CH:18]=[CH:17][C:14]1[CH:15]=[CH:16][C:11]([NH:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:9])=[O:8])=[CH:12][CH:13]=1

Participants

7

Reactant 5

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67499725HCID 67499725, compound

Product 1

HCID 41513-(4-Benzenesulfonylaminophenyl)-N-hydroxyacrylamideYield 55.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 35 (200 mg, 0.660 mmol) in DMF (10 mL) at room temperature were added 1-(3-Dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDCI, 151 mg, 0.79 mmol), and 1-Hydroxybenzotriazole hydrate (HOBT, 134 mg, 0.99 mmol). The mixture was stirred 20 min. at room temperature then NH2OTHP (116 mg, 0.99 mmol) was added. The resulting mixture was heated at 50° C. for 24 h then the DMF solvent was evaporated under reduced pressure and the residue was dissolved in CH2Cl2, washed with 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 Hexane/acetone (7:3) as solvent mixture. The residue was then dissolved in MeOH (10 mL) then 10-camphorsulfonic acid (CSA, 77 mg, 0.33 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 product was purified by flash chromatography using CH2Cl2/MeOH (9:1) as solvent mixture giving compound 36 (116 mg, 55%) as a orange solid.

Workup

  1. temperatureThe resulting mixture was heated at 50° C. for 24 h
  2. customthe DMF solvent was evaporated under reduced pressure
  3. dissolutionthe residue was dissolved in CH2Cl2
  4. washwashed with a saturated aqueous solution of NaHCO3
  5. dry with materialThe combined organic extracts were dried over (MgSO4)
  6. customcondensed
  7. customThe crude compound was purified by flash chromatography
  8. dissolutionThe residue was then dissolved in MeOH (10 mL)
  9. stirringThe mixture was stirred 2 h at room temperature
  10. customthe solvents were evaporated under reduced pressure at room temperature
  11. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-f9c5e5d28c754fca876244cda9874a8d
Source dataset
uspto-grants-2014_08
Patent number
US08796330B2

Reaction notes

Loading…