Acetic Acid → (5)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate

HRID 930355ノート

反応式

HRID 930355 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]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:5]([F:27])=[C:4]([Si](CC)(CC)CC)[CH:3]=1.BrC1N=C([C@](N[S@@](C(C)(C)C)=O)(C(F)F)CC(OC(C)(C)C)=O)C(F)=C([Si](CC)(CC)CC)C=1.[F-].[K+].C(O)(=O)C.C([O-])(O)=O.[Na+].BrC1N=C([C@@](N[S@@](C(C)(C)C)=O)(C(F)F)CC(OC(C)(C)C)=O)C(F)=CC=1>O.CN(C=O)C.C1COCC1>[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:18])[F:19])[CH2:9][C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])[C:5]([F:27])=[CH:4][CH:3]=1

参加物

10

反応物 6

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 522689Potassium FluorideHCID 86732173(R)-tert-butyl 3-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-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 131735148(5)-tert-butyl 3-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate

生成物 1

HCID 86732172(5)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate収率 98%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a polypropylene flask and cap was added a mixture of (R)-tert-butyl 3-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate and (5)-tert-butyl 3-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate (0.411 g, 0.699 mmol), THF (3 mL) and DMF (3.0 mL). To the solution was added potassium fluoride (0.112 g, 1.923 mmol) and acetic acid (0.110 mL, 1.923 mmol). The reaction mixture was stirred at rt for 18 h. The solution was poured into sat NaHCO3 (25 mL) and diluted with water (25 mL). The solution was extracted with EtOAc (2×50 mL). The combined extracts were washed with water and brine and then dried (Na2SO4) and concentrated to give a 3:1 mixture of (R)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate and (S)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4,4-difluorobutanoate (0.324 g, 0.684 mmol, 98% yield) as a colorless oil. This material was used directly in the following step. MS m/z=473, 475 M+, Calculated for C17H24BrF3N2O3S: 473.35.

後処理

  1. customTo a polypropylene flask and cap
  2. additionwas added
  3. additionThe solution was poured
  4. extractionThe solution was extracted with EtOAc (2×50 mL)
  5. washThe combined extracts were washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customto give

出典と根拠

ORDレコード
ord-6e2faa9c4a584f7698e6733af208f2ed
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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