Sulfuric Acid → (2S)-N-hydroxy-2-{[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}phenyl)carbonyl](methyl)amino}-N',2-dimethylpropanediamide

HRID 1519719Notes

Reaction equation

HRID 1519719 reaction equation
S(=O)(=O)(O)O.[CH3:6][O:7][CH2:8][C:9]1[O:13][CH:12]=[C:11]([C:14]#[C:15][C:16]2[CH:41]=[CH:40][C:19]([C:20]([N:22]([CH3:39])[C@:23]([CH3:38])([C:28]([NH:30][O:31]C3CCCCO3)=[O:29])[C:24]([NH:26][CH3:27])=[O:25])=[O:21])=[CH:18][CH:17]=2)[CH:10]=1.C(=O)([O-])O.[Na+].[Cl-].[Na+]>O.C(OCC)(=O)C.O1CCOCC1>[OH:31][NH:30][C:28](=[O:29])[C@:23]([N:22]([C:20]([C:19]1[CH:40]=[CH:41][C:16]([C:15]#[C:14][C:11]2[CH:10]=[C:9]([CH2:8][O:7][CH3:6])[O:13][CH:12]=2)=[CH:17][CH:18]=1)=[O:21])[CH3:39])([CH3:38])[C:24]([NH:26][CH3:27])=[O:25]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 5234Sodium ChlorideHCID 516892Sodium BicarbonateHCID 86679283(2S)-2-[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}benzoyl)(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

Product 1

HCID 86679284(2S)-N-hydroxy-2-{[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}phenyl)carbonyl](methyl)amino}-N',2-dimethylpropanediamideYield 70%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A 1 mol/L sulfuric acid aqueous solution (2.6 mL) was added dropwise, under water cooling, to a 1,4-dioxane (4.0 mL) solution of (2S)-2-[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}benzoyl)(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (0.43 g) as obtained in Example 18-(4), and the mixture was stirred for 3 hours and 45 minutes at room temperature. Ethyl acetate and water were added, and the mixture was adjusted to pH 6 with a saturated aqueous solution of sodium hydrogen carbonate. Then, sodium chloride was added, and the organic layer was isolated. The extract was washed with brine, and dried over anhydrous sodium sulfate. Then, the desiccant was filtered out, and the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=100/0→80/20) to obtain (2S)-N-hydroxy-2-{[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}phenyl)carbonyl](methyl)amino}-N′,2-dimethylpropanediamide (Compound 550, white solid) (0.25 g, 68%).

Workup

  1. customthe organic layer was isolated
  2. washThe extract was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThen, the desiccant was filtered out
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/methanol=100/0→80/20)

Sources & evidence

ORD record
ord-2e38d95c0119441aac9bc1ea3d2b3f8b
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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