1,4-Butanediol → Ethyl 3-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-7,12-dioxaspiro[5.6]dodec-1-ene-2-carboxylate

HRID 546352Notes

Reaction equation

HRID 546352 reaction equation
[CH2:1](O)[CH2:2]CCO.C(O[Si](C)(C)C)(C)C.[Cl:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[NH:23][S:24]([CH:27]1[C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:31][C:30]([O:40][CH3:41])([O:38][CH3:39])[CH2:29][CH2:28]1)(=[O:26])=[O:25].FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(=O)([O-])O.[Na+]>ClCCl>[Cl:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[NH:23][S:24]([CH:27]1[CH2:28][CH2:29][C:30]2([O:38][CH2:39][CH2:2][CH2:1][CH2:41][O:40]2)[CH:31]=[C:32]1[C:33]([O:35][CH2:36][CH3:37])=[O:34])(=[O:25])=[O:26]

Participants

7

Reactant 5

HCID 80641,4-ButanediolHCID 65367Trimethylsilyl triflateHCID 74578Trimethyl(1-methylethoxy)silaneHCID 516892Sodium BicarbonateHCID 67192731Ethyl 6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-3,3-dimethoxy-1-cyclohexene-1-carboxylate

Product 1

HCID 57870969Ethyl 3-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-7,12-dioxaspiro[5.6]dodec-1-ene-2-carboxylateYield 3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

34 mg (0.61 mmol) of 1,4-butanediol was dissolved in 5 ml of dichloromethane, 0.32 ml (1.83 mmol) of isopropoxytrimethylsilane, and 200 mg (0.47 mmol) of ethyl 6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-3,3-dimethoxy-1-cyclohexene-1-carboxylate obtained in Example (16a) and 4 μl (0.024 mmol) of trimethylsilyl trifluoromethanesulfonate were sequentially added thereto with stirring under ice-cooling, followed by stirring for 2 hours at the same temperature. Saturated aqueous sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The residue was subjected to silica gel column chromatography (solvent; hexane:ethyl acetate=3:1), and the resulting solid was further washed with hexane to give 6 mg of the title compound as a white powder (yield: 3%).

Workup

  1. temperaturecooling
  2. stirringby stirring for 2 hours at the same temperature
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationfollowed by concentration under reduced pressure
  7. washthe resulting solid was further washed with hexane

Sources & evidence

ORD record
ord-50a6693c47354f19909f08b266755fd9
Source dataset
uspto-grants-2011_05
Patent number
US07935835B2

Reaction notes

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