Hydroxyamine hydrochloride → sodium 1-[4-[(1R,3E)-3-hydroxyimino-3-(1-methyl-6-oxo-3-pyridinyl)-1-(2-methylphenyl)propyl]phenyl]piperidine-4-carboxylate

HRID 1618049Notes

Reaction equation

HRID 1618049 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[CH:5][C:4]([C:9](=O)[CH2:10][C@H:11]([C:19]2[CH:24]=[CH:23][C:22]([N:25]3[CH2:30][CH2:29][CH:28]([C:31]([OH:33])=[O:32])[CH2:27][CH2:26]3)=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])=[CH:3]1.Cl.[NH2:36][OH:37].C(=O)([O-])O.[Na+:42]>C(O)C.O>[OH:37]/[N:36]=[C:9](/[C:4]1[CH:5]=[CH:6][C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1)\[CH2:10][C@H:11]([C:19]1[CH:20]=[CH:21][C:22]([N:25]2[CH2:30][CH2:29][CH:28]([C:31]([O-:33])=[O:32])[CH2:27][CH2:26]2)=[CH:23][CH:24]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH3:18].[Na+:42]

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochloride2×HCID 516892Sodium Bicarbonate2×HCID 66668769(R)-1-(4-(3-(1-Methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-oxo-1-o-tolylpropyl)phenyl)piperidine-4-carboxylic acid

Product 1

HCID 87237013sodium 1-[4-[(1R,3E)-3-hydroxyimino-3-(1-methyl-6-oxo-3-pyridinyl)-1-(2-methylphenyl)propyl]phenyl]piperidine-4-carboxylateYield 61.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a microwave vial was added (R)-1-(4-(3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-oxo-1-o-tolylpropyl)phenyl)piperidine-4-carboxylic acid (100 mg, 218 μmol), hydroxylamine hydrochloride (45.5 mg, 654 μmol) and sodium hydrogencarbonate (91.6 mg, 1.09 mmol) in ethanol (2 mL) and water (0.2 mL). The vial was capped and heated at 120° C. for 15 min, then hydroxylamine hydrochloride (45.5 mg, 654 μmol) and sodium hydrogencarbonate (91.6 mg, 1.09 mmol) were added again. The vial was capped and heated at 120° C. for 10 min, then the reaction mixture was evaporated. The residue was washed with dichloromethane, then suspended in dichloromethane/methanol 9:1 and filtered. The filtrate was concentrated and purified by chromatography (SiO2; gradient dichloromethane/methanol 19:1 to dichloro-methane/methanol 4:1) to afford the title compound (66 mg, 61%). Light brown solid, MS (ESI−): m/z=472.4 (M−H)−.

Workup

  1. customThe vial was capped
  2. customThe vial was capped
  3. temperatureheated at 120° C. for 10 min
  4. customthe reaction mixture was evaporated
  5. washThe residue was washed with dichloromethane
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. custompurified by chromatography (SiO2; gradient dichloromethane/methanol 19:1 to dichloro-methane/methanol 4:1)

Sources & evidence

ORD record
ord-b06cb6e2dfbd42ca934244b4c181a36f
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

Loading…