Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → (2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

HRID 84269Notes

Reaction equation

HRID 84269 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])[C:3]=1[F:34].CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>C(O)C.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])[C:3]=1[F:34]

Participants

5

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 86671949(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 53247213(2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamideYield 48.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

To a heterogeneous mixture of (2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (14500 mg, 26.94 mmol) in Ethanol (50 mL) and water (100 mL) was added a solution of PPTS (pyridinium p-touluenesulfonate) (7090 mg, 27.9 mmol). The mixture was stirred overnight at 70° C. and a solid formed. The solid was collected via filtration and dried to furnish the title compound as a white solid (5.7 g, 46.9%). The filtrate was concentrated to half the volume and more desired product formed and was collected via filtration to provide additional title compound (3.3 g, 27.1%). LCMS m/z 435.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55 (s, 3 H) 2.06-2.20 (m, 1 H) 2.36-2.45 (m, 1 H) 3.08 (s, 3 H) 3.67-3.81 (m, 1 H) 4.10 (ddd, J=12.20, 11.32, 4.78 Hz, 1 H) 6.47 (dt, J=7.17, 1.98 Hz, 1 H) 6.57-6.62 (m, 1 H) 7.39-7.47 (m, 1 H) 7.49-7.57 (m, 1 H) 7.77 (d, J=7.22 Hz, 1 H) 9.23 (br. s., 1 H) 11.08 (s, 1 H) 19F NMR (376 MHz, DMSO-d6) δ ppm −138.08 (dd, J=22.56, 7.52 Hz)-139.09 (dd, J=22.56, 7.52 Hz).

Workup

  1. customa solid formed
  2. filtrationThe solid was collected via filtration
  3. customdried

Sources & evidence

ORD record
ord-44fbfe7b64e74d1b9807dde47004f631
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Reaction notes

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