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

HRID 930355Notes

Reaction equation

HRID 930355 reaction equation
[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

Participants

10

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-6e2faa9c4a584f7698e6733af208f2ed
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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