Dimethyl Sulfoxide → 2-(3-But-3-enyloxy-5-trifluoromethyl-phenyl)-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-carboxylic acid tert-butyl ester

HRID 1755098Notes

Reaction equation

HRID 1755098 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([NH:16][C:17](=O)[C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([O:28][CH2:29][CH2:30][CH:31]=[CH2:32])[CH:19]=2)([C:14]#[N:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].OO.CS(C)=[O:40]>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2([N:16]=[C:17]([C:18]3[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([O:28][CH2:29][CH2:30][CH:31]=[CH2:32])[CH:19]=3)[NH:15][C:14]2=[O:40])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 668185224-(3-But-3-enyloxy-5-trifluoromethyl-benzoylamino)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 668182902-(3-But-3-enyloxy-5-trifluoromethyl-phenyl)-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-carboxylic acid tert-butyl esterYield 67%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

4-(3-But-3-enyloxy-5-trifluoromethyl-benzoylamino)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (3.0 g) was dissolved in ethanol, and a 5 N aqueous sodium hydroxide solution (6.9 ml, 34.5 mmol) and a 30% aqueous hydrogen peroxide solution (3 ml) were added. After stirring at room temperature for two hours, DMSO (19 ml) was added to the reaction solution, and the mixture was stirred at 50° C. for four hours. The reaction solution was cooled, and then quenched with a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was sequentially washed with a saturated aqueous ammonium chloride solution, water and saturated brine, and then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 2-(3-but-3-enyloxy-5-trifluoromethyl-phenyl)-4-oxo-1,3,8-triaza-spiro[4.5]dec-1-ene-8-carboxylic acid tert-butyl ester (2.39 g, 67% in two steps).

Workup

  1. stirringthe mixture was stirred at 50° C. for four hours
  2. temperatureThe reaction solution was cooled
  3. customquenched with a saturated aqueous ammonium chloride solution
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was sequentially washed with a saturated aqueous ammonium chloride solution, water and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-843c7cba4bb64f8ebf7e942859497124
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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