Sodium Hydroxide → 2-(2-Difluoromethoxy-benzylsulfonylmethyl)-4-morpholin-4-yl-4-oxo-butyric acid

HRID 1830155노트

반응식

HRID 1830155 반응식
[N:1]1([C:7](=[O:24])[CH2:8][CH:9]([CH2:13][S:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:16])=[O:15])[C:10]([OH:12])=[O:11])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[OH-].[Na+].[F:27][CH:28]([F:38])[O:29]C1C=CC=CC=1CBr.OOS([O-])=O.[K+]>CCO.O>[F:27][CH:28]([F:38])[O:29][C:23]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:17][S:14]([CH2:13][CH:9]([CH2:8][C:7]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[O:24])[C:10]([OH:12])=[O:11])(=[O:15])=[O:16]

참가 물질

7

반응물 4

HCID 14798Sodium HydroxideHCID 27369982-(Difluoromethoxy)benzyl bromideHCID 220539874-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acidHCID 23707502Potassium hydroxy sulfite

생성물 1

HCID 220540252-(2-Difluoromethoxy-benzylsulfonylmethyl)-4-morpholin-4-yl-4-oxo-butyric acid

시약·촉매·용매 2

HCID 702Ethanol용매HCID 962Water용매

실험 절차

4-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (1.27 g, 4.64 mmol) was dissolved in 50 mL dry EtOH and set to stir at room temperature. NaOH pellets (556 mg, 13.92 mmol) were added in one portion, and the reaction mixture was allowed to stir for 10 min. 2-(Difluoromethoxy)-benzyl bromide (1.00 g, 4.219 mmol) was then added, and the reaction mixture was allowed to stir at ambient temperature for 20 h. Upon completion (LCMS), the reaction mixture was diluted with water and the pH was lowered to ˜2. The reaction mixture was then washed 3× with EtOAc. The organic phase was concentrated in vacuo and then diluted with 100 mL aqueous MeOH. Oxone (1.58 g, 2.43 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: 195 mg, 19.0%. m/z (LCMS) M+ 422.1. Rf=2.42. δH 12.6 (1H, br s), 7.6–7.2 (4H, m), 7.19 (1H, s) 4.5 (2H, s), 3.5 (4H, m), 3.5 (1H, m), 3.4 (4H, m), 3.2 (2H, d), 2.75 (2H, d).

후처리

  1. additionwere added in one portion
  2. stirringto stir for 10 min
  3. stirringto stir at ambient temperature for 20 h
  4. washThe reaction mixture was then washed 3× with EtOAc
  5. concentrationThe organic phase was concentrated in vacuo
  6. additiondiluted with 100 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

출처 및 근거

ORD 기록
ord-323005841f174ee89a610804e5eb9688
출처 데이터셋
uspto-grants-2006_06
특허 번호
US07064123B1

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