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

HRID 709246Notes

Reaction equation

HRID 709246 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N:12]([CH2:15][CH2:16][C@@:17]([CH3:32])([S:28]([CH3:31])(=[O:30])=[O:29])[C:18]([NH:20][O:21]C3CCCCO3)=[O:19])[C:11](=[O:33])[CH:10]=2)=[CH:5][CH:4]=1>CC(O)C>[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N:12]([CH2:15][CH2:16][C@@:17]([CH3:32])([S:28]([CH3:31])(=[O:29])=[O:30])[C:18]([NH:20][OH:21])=[O:19])[C:11](=[O:33])[CH:10]=2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86671944(2R)-4-[4-(4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 57326989(2R)-4-[4-(4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 1.0 M aqueous HCl (2.76 mL) was added slowly to a solution of (2R)-4-[4-(4-fluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (257 mg, 0.55 mmol) in 2-propanol (15 mL) at room temperature. The reaction was allowed to stir at room temperature overnight. After 18 hours the reaction was concentrated to afford a brown solid. Crude material was triturated in ethyl acetate (50 mL) for 1 hour; the solid was collected via filtration and washed with hexanes (20 mL). The solid was allowed to dry on the filter under high vacuum to afford an off-white solid. Yield 153 mg, 73%. MS (APCI) m/z 383.6 (M+H), 1H NMR (400 MHz, DMSO-d6) δ ppm 1.55 (s, 3H) 2.08-2.19 (m, 1H) 2.34-2.44 (m, 1H) 3.08 (s, 3H) 3.64-3.80 (m, 1H) 4.04-4.13 (m, 1H) 6.62 (dd, J=7.02, 2.15 Hz, 1H) 6.67 (d, J=1.95 Hz, 1H) 7.20-7.41 (m, 2H) 7.64-7.84 (m, 3H) 11.12 (br. s., 1H)

Workup

  1. concentrationAfter 18 hours the reaction was concentrated
  2. customto afford a brown solid
  3. customCrude material was triturated in ethyl acetate (50 mL) for 1 hour
  4. filtrationthe solid was collected via filtration
  5. washwashed with hexanes (20 mL)
  6. customto dry on the
  7. filtrationfilter under high vacuum
  8. customto afford an off-white solid

Sources & evidence

ORD record
ord-524fe34b1aad4bb5b2fb194bae8656ed
Source dataset
uspto-grants-2015_11
Patent number
US09180123B2

Reaction notes

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