Tetrahydrofuran → (R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide

HRID 930356노트

반응식

HRID 930356 반응식
[Br:1][C:2]1[N:7]=[C:6]([C@@:8]([NH:20][S@@:21]([C:23]([CH3:26])([CH3:25])[CH3:24])=[O:22])([CH:17]([F:19])[F:18])[CH2:9][C:10](OC(C)(C)C)=[O:11])[C:5]([F:27])=[CH:4][CH:3]=1.BrC1N=C([C@](N[S@@](C(C)(C)C)=O)(C(F)F)CC(OC(C)(C)C)=O)C(F)=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+].BrC1N=C([C@](N[S@@](C(C)(C)C)=O)(CCO)C(F)F)C(F)=CC=1>C(Cl)Cl>[Br:1][C:2]1[N:7]=[C:6]([C@@:8]([NH:20][S@@:21]([C:23]([CH3:25])([CH3:24])[CH3:26])=[O:22])([CH2:9][CH2:10][OH:11])[CH:17]([F:19])[F:18])[C:5]([F:27])=[CH:4][CH:3]=1

참가 물질

8

반응물 6

HCID 8028TetrahydrofuranHCID 62649Sodium sulfate decahydrateHCID 21226445Aluminium lithium hydrideHCID 86732172(5)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoateHCID 86732174(R)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoateHCID 86732176(R)-N-((R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide

생성물 1

HCID 86732175(R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide수율 62.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
-10 °C

실험 절차

To a 100-mL round-bottomed flask were added a mixture of (R)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate and (5)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate (0.33 g, 0.697 mmol) and DCM (6.97 ml). The solution was cooled to −10° C. and lithium aluminum hydride, 1.0m solution in THF (1.394 ml, 1.394 mmol) was added dropwise over 10 min. The reaction mixture was stirred −10° C. for 4 h. Sodium sulfate decahydrate (1.8 g, 5.6 mmol) was added and the mixture was stirred for 10 min. The solid was filtered and washed with EtOAc. The filtrate was concentrated in vacuo. Purification by silica gel chromatography (0-70% EtOAc/hexane) afforded a 3:1 mixture of (R)-N-((R)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide and (R)-N-((S)-2-(6-bromo-3-fluoropyridin-2-yl)-1,1-difluoro-4-hydroxybutan-2-yl)-2-methylpropane-2-sulfinamide (0.176 g, 0.436 mmol, 62.6% yield) as a colorless oil. MS m/z=403, 405 M+ Calculated for C13H18BrF3N2O2S: 403.26. Used directly in the following step.

후처리

  1. additionTo a 100-mL round-bottomed flask were added
  2. stirringthe mixture was stirred for 10 min
  3. filtrationThe solid was filtered
  4. washwashed with EtOAc
  5. concentrationThe filtrate was concentrated in vacuo
  6. customPurification by silica gel chromatography (0-70% EtOAc/hexane)
  7. customafforded

출처 및 근거

ORD 기록
ord-e5e28ddf851a48fb944c4a74e2a3b83d
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296734B2

반응 노트

불러오는 중…