Acetic Acid → (R)-3-(6-Bromo-3-fluoro-pyridin-2-yl)-2,2-difluoro-3-((R)-2-methyl-propane-2-sulfinylamino)-butyric acid ethyl ester

HRID 1752457Notes

Reaction equation

HRID 1752457 reaction equation
[F-].[K+].[CH2:3]([O:5][C:6](=[O:34])[C:7]([F:33])([F:32])[C@@:8]([C:17]1[C:22]([F:23])=[C:21]([Si](CC)(CC)CC)[CH:20]=[C:19]([Br:31])[N:18]=1)([NH:10][S@@:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])[CH3:9])[CH3:4].C(O)(=O)C.CN(C=O)C>C1COCC1.C(OCC)(=O)C>[CH2:3]([O:5][C:6](=[O:34])[C:7]([F:32])([F:33])[C@@:8]([C:17]1[C:22]([F:23])=[CH:21][CH:20]=[C:19]([Br:31])[N:18]=1)([NH:10][S@@:11]([C:13]([CH3:16])([CH3:14])[CH3:15])=[O:12])[CH3:9])[CH3:4]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 522689Potassium FluorideHCID 86689143(R)-3-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-2,2-difluoro-3-((R)-2-methyl-propane-2-sulfinylamino)-butyric acid ethyl ester

Product 1

HCID 86689142(R)-3-(6-Bromo-3-fluoro-pyridin-2-yl)-2,2-difluoro-3-((R)-2-methyl-propane-2-sulfinylamino)-butyric acid ethyl esterYield 88%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Freshly ground KF (195 mg, 3.36 mmol) was added to a solution of (R)-3-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-2,2-difluoro-3-((R)-2-methyl-propane-2-sulfinylamino)-butyric acid ethyl ester (940 mg, 1.68 mmol) and acetic acid (0.192 ml, 3.36 mmol) in THF (7 ml). DMF (7 ml) was added and the suspension was stirred at rt. After 2 h the reaction mixture was diluted with ethyl acetate and washed with sat. sodium bicarbonate solution and brine, dried over sodium sulfate, filtered and evaporated. The crude product (733 mg) was chromatographed over silica gel (cyclohexane/ethyl acetate 7:3) to give the title compound as a slightly yellow oil. 664 mg (88% yield).

Workup

  1. washwashed with sat. sodium bicarbonate solution and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product (733 mg) was chromatographed over silica gel (cyclohexane/ethyl acetate 7:3)

Sources & evidence

ORD record
ord-a8047e20f19b43c3910a9efe2e51bfec
Source dataset
uspto-grants-2015_10
Patent number
US09163011B2

Reaction notes

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