Methanol → {[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-thiophen-2-yl-acetic acid methyl ester

HRID 1625476Notes

Reaction equation

HRID 1625476 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:25]=[CH:26][C:27]=1[F:28])[CH2:5][N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([NH:14][CH:15]([C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)[C:16]([OH:18])=[O:17])=[O:13])[C:7]1=[O:24].[CH3:29]O.S(Cl)(Cl)=O>>[CH3:29][O:17][C:16](=[O:18])[CH:15]([NH:14][C:12]([C:8]1[C:7](=[O:24])[N:6]([CH2:5][C:4]2[CH:25]=[CH:26][C:27]([F:28])=[C:2]([F:1])[CH:3]=2)[CH:11]=[CH:10][CH:9]=1)=[O:13])[C:19]1[S:20][CH:21]=[CH:22][CH:23]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 68609732{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-thiophen-2-yl-acetic acid

Product 1

HCID 68610280{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-thiophen-2-yl-acetic acid methyl ester

Procedure

{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-thiophen-2-yl-acetic acid (0.360 g, 0.000890 mol;) was dissolved in Methanol (10 mL, 0.2 mol;) then cooled to 0. Thionyl chloride (325 uL, 0.00445 mol;) was added and the reaction was allowed to stir o/n. The crude was concentrated then dissolved in ethyl acetate and washed with 1× citric acid, 1× saturated bicarbonate, and 1× brine. The ethyl acetate was then dried with magnesium sulfate and concentrated. The crude was then dissolved in methylene chloride and injected onto the combiflash for purification. The compound eluted at almost 100% EA using a 0-100% hexanes ethyl acetate gradient. Pure fractions were concentrated to give the pure product. ES (+) MS m/e=418.86.

Workup

  1. temperaturethen cooled to 0
  2. concentrationThe crude was concentrated
  3. dissolutionthen dissolved in ethyl acetate
  4. washwashed with 1× citric acid, 1× saturated bicarbonate, and 1× brine
  5. dry with materialThe ethyl acetate was then dried with magnesium sulfate
  6. concentrationconcentrated
  7. dissolutionThe crude was then dissolved in methylene chloride
  8. custominjected onto the combiflash for purification
  9. washThe compound eluted at almost 100% EA using a 0-100% hexanes ethyl acetate gradient
  10. concentrationPure fractions were concentrated
  11. customto give the pure product

Sources & evidence

ORD record
ord-8e548e7aa42f476cb9d48cb76e13fbfe
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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