Acetic Acid → N-[4-chloro-2-(1-cyclohexylmethoxyiminopropyl)phenyl]trifluoromethanesulfonamide

HRID 602605Notes

Reaction equation

HRID 602605 reaction equation
CN(C)CCN.[CH:7]1([CH2:13][O:14][N:15]2C(=O)C3=CC=CC=C3C2=O)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.C(O)(=O)C.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([NH:37][S:38]([C:41]([F:44])([F:43])[F:42])(=[O:40])=[O:39])=[C:33]([C:45](=O)[CH2:46][CH3:47])[CH:32]=1>CCO>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([NH:37][S:38]([C:41]([F:44])([F:43])[F:42])(=[O:40])=[O:39])=[C:33]([C:45](=[N:15][O:14][CH2:13][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:46][CH3:47])[CH:32]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 66053N,N-DimethylethylenediamineHCID 140744162-(cyclohexylmethoxy)-1H-isoindole-1,3(2H)-dioneHCID 67269822N-(4-chloro-2-propionylphenyl)trifluoromethanesulfonamide

Product 1

HCID 86604003N-[4-chloro-2-(1-cyclohexylmethoxyiminopropyl)phenyl]trifluoromethanesulfonamideYield 91.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

N,N-Dimethylethylenediamine (1.53 mL, 13.18 mmol) was added to a solution of N-(cyclohexylmethoxy)phthalimide (2.33 g, 8.99 mmol) in EtOH (30 mL), and the reaction allowed to stir at RT for 2 hours. Glacial acetic acid (5 mL) was then added to adjust the mixture to ca. pH 4 followed by a solution of N-(4-chloro-2-propionylphenyl)trifluoromethanesulfonamide 22 (1.89 g, 5.99 mmol) in EtOH (10 mL), and the reaction stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, and the residue dissolved in Et2O (50 mL) and washed with water, brine, dried over MgSO4 and the solvent removed under reduced pressure. The residue was purified by column chromatography (eluting with CH2Cl21PE, 3:4 to 1:3) to afford N-[4-chloro-2-(1-cyclohexylmethoxyiminopropyl)phenyl]trifluoromethanesulfonamide 104 (2.34 g, 91%), as colorless crystals. 1H n.m.r. (400 MHz, CDCl3) δ 12.01, br s, 1H, 7.67, d, J=8.8 Hz, 1H, 7.48, d, J=2.4 Hz, 1H, 7.32, dd, J=2.4 and 8.8 Hz, 1H, 4.02, d, J=6 Hz, 2H, 2.81, q, J=7.6 Hz, 2H, 1.74, m, 6H, 1.27, m, 3H; 1.19, t, J=7.6 Hz, 3H, 1.01, m, 2H. HRMS (M+) 426.0971.

Workup

  1. stirringthe reaction stirred for 15 hours at RT
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. dissolutionthe residue dissolved in Et2O (50 mL)
  4. washwashed with water, brine
  5. dry with materialdried over MgSO4
  6. customthe solvent removed under reduced pressure
  7. customThe residue was purified by column chromatography (eluting with CH2Cl21PE, 3:4 to 1:3)

Sources & evidence

ORD record
ord-63a5979470a840e288fa441025c30529
Source dataset
uspto-grants-2011_03
Patent number
US07906538B2

Reaction notes

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