p-Toluenesulfonic acid → HCID 19434003, compound

HRID 1736019Notes

Reaction equation

HRID 1736019 reaction equation
O1CC[O:3][CH:2]1[C:6]1[CH:10]=[CH:9][S:8][C:7]=1[S:11]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)(=[O:13])=[O:12].[H-].[Na+].Br[CH2:26][C:27]([O:29][CH3:30])=[O:28].C(=O)(O)[O-].[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.CN(C=O)C.CC(C)=O.O>[CH3:30][O:29][C:27](=[O:28])[CH2:26][N:14]([S:11]([C:7]1[S:8][CH:9]=[CH:10][C:6]=1[CH:2]=[O:3])(=[O:12])=[O:13])[C:15]1[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=1

Participants

11

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 10340Sodium CarbonateHCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 516892Sodium BicarbonateHCID 19434098HCID 19434098, compound

Product 1

HCID 19434003HCID 19434003, compoundYield 33.2%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the product of Step A (10.21 g, 29.9 mmol) in anhydrous THF (100 mL) and DMF (15 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 1.32 g, 32.9 mmol). After stirring for 30 min, methyl 2-bromoacetate (5.49 g, 35.9 mmol) was added and stirring continued at ambient temperature for 4 h. The reaction mixture was poured into a saturated solution of sodium bicarbonate (150 mL) and extracted with ethyl acetate (2×100 mL). The combined extracts was dried (MgSO4) and evaporated to give an oil which was dissolved in acetone (150 mL) and p-toluenesulfonic acid (2.5 g) was added. This solution was stirred at ambient temperature for 2 h, heated at reflux temperature for 5 h, cooled and mixed with water (100 mL) and sodium carbonate (1.0 g). Acetone was evaporated and the aqueous was extracted with ethyl acetate (2×100 mL). The combined extracts were dried (MgSO4) and evaporated to a residue which was purified by column chromatography (silica, 40% ethyl acetate/hexane) to give an oil (3.67 g, 33%).

Workup

  1. stirringstirring
  2. waitcontinued at ambient temperature for 4 h
  3. extractionextracted with ethyl acetate (2×100 mL)
  4. dry with materialThe combined extracts was dried (MgSO4)
  5. customevaporated
  6. customto give an oil which
  7. stirringThis solution was stirred at ambient temperature for 2 h
  8. temperatureheated
  9. temperatureat reflux temperature for 5 h
  10. temperaturecooled
  11. customAcetone was evaporated
  12. extractionthe aqueous was extracted with ethyl acetate (2×100 mL)
  13. dry with materialThe combined extracts were dried (MgSO4)
  14. customevaporated to a residue which
  15. customwas purified by column chromatography (silica, 40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-66a1ecb87ea7463e9408ed866adc0e10
Source dataset
uspto-grants-1996_07
Patent number
US05538966

Reaction notes

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