Sulfuric Acid → (2S)-N-hydroxy-N',2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]propanediamide

HRID 1519705Notes

Reaction equation

HRID 1519705 reaction equation
S(=O)(=O)(O)O.[CH3:6][NH:7][C:8](=[O:47])[C@:9]([CH3:46])([N:20]([CH3:45])[C:21](=[O:44])[C:22]1[CH:27]=[CH:26][C:25]([C:28]#[C:29][C:30]2[CH:35]=[CH:34][C:33]([CH2:36][N:37]3[CH2:43][CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[CH:32][CH:31]=2)=[CH:24][CH:23]=1)[C:10]([NH:12][O:13]C1CCCCO1)=[O:11].[OH-].[Na+].C(=O)([O-])O.[Na+].[Cl-].[Na+]>C(OCC)(=O)C.O.O1CCOCC1>[OH:13][NH:12][C:10](=[O:11])[C@@:9]([CH3:46])([N:20]([CH3:45])[C:21](=[O:44])[C:22]1[CH:23]=[CH:24][C:25]([C:28]#[C:29][C:30]2[CH:35]=[CH:34][C:33]([CH2:36][N:37]3[CH2:43][CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[CH:32][CH:31]=2)=[CH:26][CH:27]=1)[C:8]([NH:7][CH3:6])=[O:47]

Participants

9

Reactant 5

HCID 1118Sulfuric AcidHCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 86679271(2S)-N,2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

Product 1

HCID 71598567(2S)-N-hydroxy-N',2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]propanediamideYield 66.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A 1 mol/L sulfuric acid aqueous solution (16 mL) was added dropwise, under water cooling, to a 1,4-dioxane (6.0 mL) suspension of (2S)-N,2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (3.0 g) as obtained in Example 16-(2), and the mixture was stirred for 2 hours and 50 minutes at room temperature. Water and ethyl acetate were added, and the aqueous layer was isolated. The isolate was adjusted to pH 7 with 20% sodium hydroxide and a saturated aqueous solution of sodium hydrogen carbonate, and then ethyl acetate and sodium chloride were added, followed by isolating the organic layer. 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/acetone=100/0→60/40, followed by gradient elution with chloroform/methanol=98/2→90/10) to obtain (2S)-N-hydroxy-N′,2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]propanediamide (Compound 376, pale yellow solid) (1.7 g, 65%).

Workup

  1. customthe aqueous layer was isolated
  2. customby isolating the organic layer
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThen, the desiccant was filtered out
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/acetone=100/0→60/40, followed by gradient elution with chloroform/methanol=98/2→90/10)

Sources & evidence

ORD record
ord-0bd826279f764bc3a9d947e6c8d75a70
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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