Hydrochloric Acid → (2R)-4-[4-(4-Chloro-2-fluorophenyl)-5-fluoro-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

HRID 1625030Notes

Reaction equation

O.Cl.[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15]([F:16])=[CH:14][N:13]([CH2:17][CH2:18][C@@:19]([CH3:34])([S:30]([CH3:33])(=[O:32])=[O:31])[C:20]([NH:22][O:23]C3CCCCO3)=[O:21])[C:12](=[O:35])[CH:11]=2)=[C:6]([F:36])[CH:5]=1>C(O)C>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15]([F:16])=[CH:14][N:13]([CH2:17][CH2:18][C@@:19]([CH3:34])([S:30]([CH3:33])(=[O:32])=[O:31])[C:20]([NH:22][OH:23])=[O:21])[C:12](=[O:35])[CH:11]=2)=[C:6]([F:36])[CH:5]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Water (312 mL) and 1 N aq HCl (23.9 mL, 23.9 mmol) were added to a solution of (2R)-4-[4-(4-chloro-2-fluorophenyl)-5-fluoro-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (74.7 g, 144.1 mmol) in ethanol (126 mL). The reaction was heated to 70° C. and stirred at this temperature overnight. The reaction was allowed to cool and the solid was collected via filtration and washed with water until the filtrate had a pH of −5. The solid was dried under vacuum to afford the title compound as a white solid (46.48 g, 74%). MS (LCMS) m/z 435.6 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.56 (s, 3 H) 2.09-2.21 (m, 1 H) 2.44 (d, J=5.27 Hz, 1 H) 3.10 (s, 3 H) 3.77 (td, J=11.90, 5.07 Hz, 1 H) 4.04 (td, J=11.95, 4.98 Hz, 1 H) 6.51 (d, J=7.02 Hz, 1 H) 7.44 (dd, J=8.29, 2.05 Hz, 1 H) 7.50-7.56 (m, 1 H) 7.62 (dd, J=9.95, 1.95 Hz, 1 H) 8.04 (d, J=5.85 Hz, 1 H) 9.22 (s, 1 H) 11.05 (s, 1 H).

Workup

temperatureto cool
filtrationthe solid was collected via filtration
washwashed with water until the filtrate
customThe solid was dried under vacuum

Sources & evidence

ORD record: ord-8c0140bb35754a7ab080ceee78667152
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08779148B2

Reaction notes

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