Hydrochloric Acid → N-hydroxy-2-methyl-4-(3-methylbiphenyl-4-yl)-2(methylsulfonyl)butanamide

HRID 533516Notes

Reaction equation

HRID 533516 reaction equation
[CH3:1][C:2]([S:28]([CH3:31])(=[O:30])=[O:29])([CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][C:16]=1[CH3:27])[C:3]([NH:5][O:6]C1CCCCO1)=[O:4].Cl.O1CCOCC1.CO>ClCCl>[OH:6][NH:5][C:3](=[O:4])[C:2]([CH3:1])([S:28]([CH3:31])(=[O:29])=[O:30])[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][C:16]=1[CH3:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 312751,4-DioxaneHCID 866687562-Methyl-4-(3-methylbiphenyl-4-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 51355297N-hydroxy-2-methyl-4-(3-methylbiphenyl-4-yl)-2(methylsulfonyl)butanamideYield 6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Methyl-4-(3-methylbiphenyl-4-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (170 mg, 0.382 mmol) was dissolved in 5 mL of dichloromethane at ambient temperature. To this was added a 4M HCl solution in dioxane (2.86 mL, 11.5 mmol) and the reaction was stirred at ambient temperature for 5 minutes. 0.5 mL of methanol was then added followed by silica gel and the mixture was concentrated to dryness. Silica chromatography (100% dichloromethane to 96% DCM 4% MeOH over 60 minutes) yielded product that contained impurities and was further triturated with a solution of 4:1 heptane:isopropanol afforded the title compound as a white solid (8 mg, 6%).

Workup

  1. concentrationthe mixture was concentrated to dryness
  2. customSilica chromatography (100% dichloromethane to 96% DCM 4% MeOH over 60 minutes) yielded product that
  3. customwas further triturated with a solution of 4:1 heptane

Sources & evidence

ORD record
ord-b1812ad350b24d8aa9450eee63c2571e
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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