Formaldehyde → (+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]methyl-4-[4-(methylamino)phenyl]pyrrolidin-2-one

HRID 1838004노트

반응식

HRID 1838004 반응식
[OH:1][C@H:2]([C:17]1[S:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:20][CH:21]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=1.[CH2:28]=O.C[O-].[Na+].[BH4-].[Na+].[OH-].[Na+]>CO.O>[OH:1][C@H:2]([C:17]1[S:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:20][CH:21]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:11]=[CH:12][C:13]([NH:16][CH3:28])=[CH:14][CH:15]=1

참가 물질

8

반응물 5

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 10271018(+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-aminophenyl)-1-methylpyrrolidin-2-oneHCID 10942334Sodium Methoxide

생성물 1

HCID 59066505(+/-)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]methyl-4-[4-(methylamino)phenyl]pyrrolidin-2-one수율 76%

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

실험 절차

A mixture of (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-aminophenyl)-1-methylpyrrolidin-2-one (Example 17, 105 mg, 0.30 mmol), paraformaldehyde (13 mg, 0.42 mmol) and sodium methoxide (81 mg, 1.5 mmol) in methanol (1 mL) was stirred overnight. After adding sodium borohydride (12 mg, 0.30 mmol) the reaction mixture was heated at the reflux temperature for 1 h, then treated with a 1M NaOH solution (1 mL). The resulting mixture was stirred for 10 min, diluted with water (10 mL) and extracted with EtOAc (2×10 mL). The organic layer was washed with a saturated NaCl solution, dried (Na2SO4) and concentrated under reduced pressure to give a yellow solid. The crude product was sequentially triturated with EtOAc, Et2O and hexane to provide (±)-(4R*,5R*)-5-[(1S*)-hydroxy(5-phenyl(2-thienyl))methyl]methyl-4-[4-(methylamino)phenyl]pyrrolidin-2-one (89 mg, 76%) as a white solid: TLC (EtOAc) Rf 0.34; mp: 212° C.

후처리

  1. temperaturewas heated at the reflux temperature for 1 h
  2. stirringThe resulting mixture was stirred for 10 min
  3. extractionextracted with EtOAc (2×10 mL)
  4. washThe organic layer was washed with a saturated NaCl solution
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customto give a yellow solid
  8. customThe crude product was sequentially triturated with EtOAc, Et2O and hexane

출처 및 근거

ORD 기록
ord-c6815c49241c4635b7951d4532b033ca
출처 데이터셋
uspto-grants-2004_08
특허 번호
US06784167B2

반응 노트

불러오는 중…