Acetic Acid → HCID 90380071, compound

HRID 930344Notes

Reaction equation

HRID 930344 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:19][S@@:20]([C:22]([CH3:25])([CH3:24])[CH3:23])=[O:21])([CH2:17][F:18])[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:5]([F:26])=[C:4]([Si](CC)(CC)CC)[CH:3]=1.[F-].[K+].C(O)(=O)C.C([O-])(O)=O.[Na+]>O.CN(C=O)C.C1COCC1>[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:19][S@@:20]([C:22]([CH3:25])([CH3:24])[CH3:23])=[O:21])([CH2:17][F:18])[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:14])[CH3:15])=[O:11])[C:5]([F:26])=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 522689Potassium FluorideHCID 90373050HCID 90373050, compoundHCID 178435178HCID 178435178, compound

Product 1

HCID 90380071HCID 90380071, compoundYield 88.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a polypropylene vial with cap was added (5)-tert-butyl 3-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4-fluorobutanoate (9.8 g, 17.2 mmol), THF (50 mL) and DMF (50.0 mL). To the solution was added potassium fluoride (Aldrich; 2.75 g, 47.3 mmol) and acetic acid (2.71 mL, 47.3 mmol). The solution was stirred at rt for 17 h. The mixture was poured into sat NaHCO3 (200 mL) and then diluted with water (200 mL). The solution was extracted with EtOAc (3×100 mL) and the combined extracts were washed with water (3×100 mL) and brine (100 mL) and then dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (Gradient: 0.0 to 40% EtOAc/hexane, 120 g Silicycle column) afforded (5)-tert-butyl 3-(6-bromo-3-fluoropyridin-2-yl)-3-((R)-1,1-dimethylethylsulfinamido)-4-fluorobutanoate (6.93 g, 15.22 mmol, 88% yield) as a yellow oil. MS m/z=455.0 [M+H]+. Calculated for C17H25BrF2N2O3S: 454.1.

Workup

  1. additionThe mixture was poured
  2. extractionThe solution was extracted with EtOAc (3×100 mL)
  3. washthe combined extracts were washed with water (3×100 mL) and brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated onto silica
  6. customPurification by silica gel chromatography (Gradient: 0.0 to 40% EtOAc/hexane, 120 g Silicycle column)

Sources & evidence

ORD record
ord-189ff933b2f9411e9ff8b9c95cd87d61
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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