Trifluoroacetic acid → 4-ethoxy-3-methyl-N-(4-oxocyclohexyl)benzenesulfonamide

HRID 1944738Notes

Reaction equation

HRID 1944738 reaction equation
FC(F)(F)C(O)=O.[O:8]=[C:9]1[CH2:14][CH2:13][CH:12]([NH:15]C(=O)OC(C)(C)C)[CH2:11][CH2:10]1.CN1CCOCC1.[CH2:30]([O:32][C:33]1[CH:38]=[CH:37][C:36]([S:39](Cl)(=[O:41])=[O:40])=[CH:35][C:34]=1[CH3:43])[CH3:31]>C(Cl)Cl.CCCCCCC.C(OCC)(=O)C>[CH2:30]([O:32][C:33]1[CH:38]=[CH:37][C:36]([S:39]([NH:15][CH:12]2[CH2:11][CH2:10][C:9](=[O:8])[CH2:14][CH2:13]2)(=[O:41])=[O:40])=[CH:35][C:34]=1[CH3:43])[CH3:31]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 1512535tert-butyl N-(4-oxocyclohexyl)carbamateHCID 173898604-Ethoxy-3-methylbenzene-1-sulfonyl chloride

Product 1

HCID 672241044-ethoxy-3-methyl-N-(4-oxocyclohexyl)benzenesulfonamideYield 24.5%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

Trifluoroacetic acid (13.13 ml, 170 mmol) was added via addition funnel to solution of tert-butyl 4-oxocyclohexylcarbamate (1.817 g, 8.52 mmol) in DCM (34.1 ml) at room temperature. The reaction was stirred 3.5 hours then concentrated and the residue was placed under vacuum for 30 minutes. The residue was suspended in DCM (34.1 ml) and cooled in ice/water bath. N-methylmorpholine (20.61 ml, 187 mmol) was added followed by solid 4-ethoxy-3-methylbenzenesulfonyl chloride (2.0 g, 8.52 mmol) and the ice/water bath was removed. After stirring for 70 hours, LCMS indicated some product mass. The reaction was placed in water bath and pH adjust to 3 using 3N hydrochloric acid (aq). The resulting layers were separated, and the aqueous extracted second time with dichloromethane. The combined organics were dried over sodium sulfate to yield 2.9 g of a crude oil. TLC (50% ethyl acetate in heptane): indicated a major product at Rf=0.40, with minor spots at Rf=0.58 and Rf=0.12. The crude was chromatograph on Biotage 40M by TLC generated gradient to yield 4-ethoxy-3-methyl-N-(4-oxocyclohexyl)benzenesulfonamide (650 mg, 2.087 mmol). LCMS [M+H]=312.3.

Workup

  1. concentrationthen concentrated
  2. waitthe residue was placed under vacuum for 30 minutes
  3. temperaturecooled in ice/water bath
  4. customthe ice/water bath was removed
  5. stirringAfter stirring for 70 hours
  6. customThe resulting layers were separated
  7. dry with materialThe combined organics were dried over sodium sulfate
  8. customto yield 2.9 g of a crude oil

Sources & evidence

ORD record
ord-72b179e1a94d4f40a886e15d1f0193e9
Source dataset
uspto-grants-2013_03
Patent number
US08394858B2

Reaction notes

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