Hydrochloric Acid → (2R)-4-[5-(2-Fluoro-3-methoxyphenyl)isoxazol-3-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide butanamide

HRID 404222Notes

Reaction equation

HRID 404222 reaction equation
Cl.[F:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]1[O:15][N:14]=[C:13]([CH2:16][CH2:17][C@@:18]([CH3:33])([S:29]([CH3:32])(=[O:31])=[O:30])[C:19]([NH:21][O:22]C2CCCCO2)=[O:20])[CH:12]=1>O1CCOCC1.ClCCl.O>[C:19]([NH2:21])(=[O:20])[CH2:18][CH2:17][CH3:16].[F:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]1[O:15][N:14]=[C:13]([CH2:16][CH2:17][C@@:18]([CH3:33])([S:29]([CH3:32])(=[O:31])=[O:30])[C:19]([NH:21][OH:22])=[O:20])[CH:12]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86709154(2R)-4-[5-(2-fluoro-3-methoxyphenyl)isoxazol-3-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 86709155(2R)-4-[5-(2-Fluoro-3-methoxyphenyl)isoxazol-3-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide butanamideYield 32.5%

Reagents, catalysts & solvents 1

HCID 866687791,4 Dioxane dichloromethane waterSolvent

Procedure

Hydrochloric acid (4.0 M in 1,4-dioxane, 0.13 mL, 0.51 mmol, 4 equiv) was added to a solution of (2R)-4-[5-(2-fluoro-3-methoxyphenyl)isoxazol-3-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (0.60 g, 0.13 mmol, 1.0 equiv) in 1,4-dioxane-dichloromethane-water (2:2:1, 2.5 mL), and the reaction was allowed to stir at room temperature for 2 h. The solvent was removed under reduced pressure, and the resulting crude material purified by preparative HPLC (Sepax 2-ethyl pyridine 250×21.2 mm 5 μm, heptane-ethanol solvent system as eluent) to provide (2R)-4-[5-(2-Fluoro-3-methoxyphenyl)isoxazol-3-yl]-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide butanamide (0.01 g, 20%). MS (LCMS) m/z 385.0 (M−1). 1H NMR (400 MHz, METHONAL-d4) δ1.59-1.71 (m, 3H) 2.13-2.29 (m, 1H) 2.61-2.81 (m, 2H) 2.80-2.99 (m, 1H) 3.07 (s, 3H) 3.92 (s, 3H) 6.65-6.84 (m, 1H) 7.16-7.30 (m, 2H) 7.37-7.52 (m, 1H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe resulting crude material purified by preparative HPLC (Sepax 2-ethyl pyridine 250×21.2 mm 5 μm, heptane-ethanol solvent system as eluent)

Sources & evidence

ORD record
ord-68788bfb82bb4ea190c419ec38626c22
Source dataset
uspto-grants-2014_06
Patent number
US08748466B2

Reaction notes

Loading…