Sodium Hydroxide → 2-Cyclopropylmethanesulfonylmethyl-4-morpholin-4-yl-4-oxo-butyric acid

HRID 1830154Notes

Reaction equation

HRID 1830154 reaction equation
[N:1]1([C:7](=[O:24])[CH2:8][CH:9]([CH2:13][S:14]([CH2:17][C:18]2[CH:23]=[CH:22]C=CC=2)(=[O:16])=[O:15])[C:10]([OH:12])=[O:11])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH-].[Na+].BrCC1CC1.OOS([O-])=O.[K+]>CCO.O>[CH:18]1([CH2:17][S:14]([CH2:13][CH:9]([CH2:8][C:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)=[O:24])[C:10]([OH:12])=[O:11])(=[O:15])=[O:16])[CH2:23][CH2:22]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 81503BromomethylcyclopropaneHCID 22053987HCID 22053987, compoundHCID 23707502Potassium hydroxy sulfite

Product 1

HCID 220540982-Cyclopropylmethanesulfonylmethyl-4-morpholin-4-yl-4-oxo-butyric acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

4-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (11.16 g, 40.74 mmol) was dissolved in 100 mL dry EtOH and set to stir at room temperature. NaOH pellets (4.81 g, 120.25 mmol) were added in one portion, and the reaction mixture was allowed to stir for 10 min. Bromomethylcyclopropane (5.0 g, 37.04 mmol) was then added, and the reaction mixture was allowed to stir at ambient temperature for 20 hours. Upon completion (LCMS), the reaction mixture was diluted with water and the pH was lowered to ˜pH2. The reaction mixture was then washed 3× with EtOAc. The organic phase was concentrated in vacuo and then diluted with 200 mL aqueous MeOH. Oxone (15.6 g, 24.0 mmol) was added in one portion and the reaction was stirred at room temperature for 4 h. Conversion of sulfide to sulfone was monitored via LCMS. Upon completion, reaction was quenched by the addition of sodium thiosulfate. Salts were filtered, and the reaction mixture was washed 3× with ethyl acetate and dried over sodium sulfate. The organics were evaporated by vacuum under reduced pressure. Product was purified via HPLC. Yield: 1.2 g, 15.1%. m/z (LCMS) M+ 320.1, Rf=1.84. δH 12.6 (1H, br s), 3.5 (4H, m), 3.5 (1H, m), 3.4 (4H, m), 3.25 (2H, d), 3.0 (2H, m), 2.9 (2H, d), 2.4 (1H, m), 1.1 (1H, m), 0.62 (2H, q), 0.38 (2H, q).

Workup

  1. additionwere added in one portion
  2. stirringto stir for 10 min
  3. stirringto stir at ambient temperature for 20 hours
  4. washThe reaction mixture was then washed 3× with EtOAc
  5. concentrationThe organic phase was concentrated in vacuo
  6. additiondiluted with 200 mL aqueous MeOH
  7. stirringthe reaction was stirred at room temperature for 4 h
  8. customUpon completion, reaction
  9. customwas quenched by the addition of sodium thiosulfate
  10. filtrationSalts were filtered
  11. washthe reaction mixture was washed 3× with ethyl acetate
  12. dry with materialdried over sodium sulfate
  13. customThe organics were evaporated by vacuum under reduced pressure
  14. customProduct was purified via HPLC

Sources & evidence

ORD record
ord-b0fee5bd6ae546a99e04c5ef407edadf
Source dataset
uspto-grants-2006_06
Patent number
US07064123B1

Reaction notes

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