Trimethylsilyl triflate → ethyl (2R)-8-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-2-((4R)-2,2-dimethyl[1.3]dioxolan-4-yl)-1,4-dioxaspiro[4.5]dec-6-ene-7-carboxylate

HRID 2191155Notes

Reaction equation

HRID 2191155 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][S:10]([CH:13]1[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:17][C:16]([O:26][CH3:27])([O:24][CH3:25])[CH2:15][CH2:14]1)(=[O:12])=[O:11].[CH3:28][C:29]1([CH3:46])[O:33][C@H:32](CO[Si](C)(C)C)[C@@H:31](CO[Si](C)(C)C)[O:30]1.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(=O)([O-])O.[Na+]>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][S:10]([CH:13]1[CH2:14][CH2:15][C:16]2([O:24][C@@H:25]([C@H:31]3[CH2:32][O:33][C:29]([CH3:46])([CH3:28])[O:30]3)[CH2:27][O:26]2)[CH:17]=[C:18]1[C:19]([O:21][CH2:22][CH3:23])=[O:20])(=[O:11])=[O:12]

Participants

6

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 67189720(4R,5R)-2,2-dimethyl-4,5-bis[(trimethylsilyl)oxy]methyl[1.3]dioxolaneHCID 67192731Ethyl 6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-3,3-dimethoxy-1-cyclohexene-1-carboxylate

Product 1

HCID 67192752ethyl (2R)-8-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-2-((4R)-2,2-dimethyl[1.3]dioxolan-4-yl)-1,4-dioxaspiro[4.5]dec-6-ene-7-carboxylateYield 24.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

300 mg (0.71 mmol) of ethyl 6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-3,3-dimethoxy-1-cyclohexene-1-carboxylate obtained in Example (16a) and 436 mg (1.42 mmol) of (4R,5R)-2,2-dimethyl-4,5-bis[(trimethylsilyl)oxy]methyl[1.3]dioxolane were dissolved in 12 ml of dichloromethane and 26 μl (0.142 mmol) of trimethylsilyl trifluoromethanesulfonate was added thereto with stirring under ice-cooling, followed by stirring for 90 hours at room temperature. Saturated aqueous sodium hydrogencarbonate was added to the reaction solution and the mixture was extracted with dichloromethane. 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=4:1) to give 90 mg of ethyl (2R)-8-[N-(2-chloro-4-fluorophenyl)sulfamoyl]-2-((4R)-2,2-dimethyl[1.3]dioxolan-4-yl)-1,4-dioxaspiro[4.5]dec-6-ene-7-carboxylate as an amorphous substance (yield: 24%).

Workup

  1. temperaturecooling
  2. stirringby stirring for 90 hours at room temperature
  3. extractionthe mixture was extracted with dichloromethane
  4. washThe organic layer was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationfollowed by concentration under reduced pressure

Sources & evidence

ORD record
ord-f1674f3568ba4be1ba7812056b9f19de
Source dataset
uspto-grants-2012_12
Patent number
USRE043858E1

Reaction notes

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