Hydrochloric Acid → (2R)-4-[4-(4-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

HRID 709227Notes

Reaction equation

HRID 709227 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]([CH2:14][CH2:15][C@@:16]([CH3:31])([S:27]([CH3:30])(=[O:29])=[O:28])[C:17]([NH:19][O:20]C3CCCCO3)=[O:18])[C:10](=[O:32])[CH:9]=2)=[C:4]([F:33])[CH:3]=1.Cl>ClCCl.O1CCOCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]([CH2:14][CH2:15][C@@:16]([CH3:31])([S:27]([CH3:30])(=[O:28])=[O:29])[C:17]([NH:19][OH:20])=[O:18])[C:10](=[O:32])[CH:9]=2)=[C:4]([F:33])[CH:3]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 86671931(2R)-4-[4-(4-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 57325690(2R)-4-[4-(4-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamideYield 104.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

(2R)-4-[4-(4-chloro-2-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (1188 mg impure material, 1 mmol) was dissolved in 3 mL of dichloromethane. To this solution was added 1 mL of 4M HCl in dioxane and 1 mL of water. The reaction was monitored for completion by LCMS. Upon completion, the reaction mixture was concentrated and redissolved in a minimal amount of dimethylsulfoxide and water and loaded onto a 5 g c18 guard-column. This material was purified on a 75 g c18 column with 10-40% acetonitrile in water with 0.1% trifluoroacetic acid. The desired material was concentrated yielding 434 mg (88%) of a light yellow solid. LCMS m/z 417.5 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.58 (s, 3H) 2.10-2.23 (m, 1H) 2.37-2.47 (m, 1H) 3.11 (s, 3H) 3.69-3.82 (m, 1H) 4.04-4.19 (m, 1H) 6.44-6.52 (m, 1H) 6.58 (s, 1H) 7.42 (dd, J=8.29, 1.85 Hz, 1H) 7.56-7.67 (m, 2H) 7.77 (d, J=7.02 Hz, 1H) 11.12 (br. s., 1H)

Workup

  1. concentrationUpon completion, the reaction mixture was concentrated
  2. dissolutionredissolved in a minimal amount of dimethylsulfoxide and water
  3. customThis material was purified on a 75 g c18 column with 10-40% acetonitrile in water with 0.1% trifluoroacetic acid
  4. concentrationThe desired material was concentrated

Sources & evidence

ORD record
ord-959a6153a43f46ddafea861b9b312c8c
Source dataset
uspto-grants-2015_11
Patent number
US09180123B2

Reaction notes

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