Hydrochloric Acid → (2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

HRID 84264Notes

Reaction equation

HRID 84264 reaction equation
Cl.[F:2][C:3]1[C:8]([F:9])=[C:7]([O:10][CH3:11])[CH:6]=[CH:5][C:4]=1[C:12]1[CH:17]=[CH:16][N:15]([CH2:18][CH2:19][C@@:20]([CH3:35])([S:31]([CH3:34])(=[O:33])=[O:32])[C:21]([NH:23][O:24]C2CCCCO2)=[O:22])[C:14](=[O:36])[CH:13]=1>O1CCOCC1>[F:2][C:3]1[C:8]([F:9])=[C:7]([O:10][CH3:11])[CH:6]=[CH:5][C:4]=1[C:12]1[CH:17]=[CH:16][N:15]([CH2:18][CH2:19][C@@:20]([CH3:35])([S:31]([CH3:34])(=[O:33])=[O:32])[C:21]([NH:23][OH:24])=[O:22])[C:14](=[O:36])[CH:13]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86671946(2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 86671945(2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 1.0 M aqueous HCl (2.76 mL) was added slowly to a solution of (2R)-4-[4-(2,3-difluoro-4-methoxyphenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (132 mg, 0.26 mmol) in 1,4-dioxane (15 mL) at room temperature. The reaction was allowed to stir at room temperature overnight. After 18 hours the reaction was concentrated to 25% of the original volume, resulting in a white precipitate. The precipitate was filtered via Buchner funnel and washed with hexanes (20 mL) to afford a white solid. Yield 45 mg, 41%. MS (APCI) m/z 431.1 (M+H). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55 (s, 3 H) 2.14 (td, J=12.20, 4.88 Hz, 1 H) 2.35-2.45 (m, 1 H) 3.08 (s, 3 H) 3.72 (td, J=12.05, 4.78 Hz, 1 H) 3.90 (s, 3 H) 4.09 (td, J=11.90, 5.27 Hz, 1 H) 6.46 (dt, J=7.02, 1.85 Hz, 1 H) 6.54 (s, 1 H) 7.03-7.17 (m, 1 H) 7.37 (td, J=8.63, 2.24 Hz, 1 H) 7.72 (d, J=7.22 Hz, 1 H) 9.22 (br. s., 1 H) 11.10 (s, 1H)

Workup

  1. concentrationAfter 18 hours the reaction was concentrated to 25% of the original volume
  2. customresulting in a white precipitate
  3. filtrationThe precipitate was filtered via Buchner funnel
  4. washwashed with hexanes (20 mL)
  5. customto afford a white solid

Sources & evidence

ORD record
ord-d8c0c56d56754eeab69d02df7d5c1b7f
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Reaction notes

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