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

HRID 930356ノート

反応式

HRID 930356 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
-10 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e5e28ddf851a48fb944c4a74e2a3b83d
出典データセット
uspto-grants-2016_03
特許番号
US09296734B2

反応ノート

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