Citric Acid → HCID 50996222, compound

HRID 1026581Notes

Reaction equation

HRID 1026581 reaction equation
[Cl:1][C:2]1[CH:40]=[N:39][C:5]2[O:6][C@@H:7]([CH3:38])[C:8](=[O:37])[N:9]([CH:10]3[CH2:15][CH2:14][N:13]([C:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[O:30][CH2:31][C@H:32]([CH3:35])[CH2:33][OH:34])=[CH:20][C:19]=4[F:36])=[O:17])[CH2:12][CH2:11]3)[C:4]=2[CH:3]=1.P([O-])([O-])([O-])=[O:42].Cl([O-])=O.[Na+].Cl[O-].[Na+].S([O-])([O-])=O.[Na+].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(#N)C>[Cl:1][C:2]1[CH:40]=[N:39][C:5]2[O:6][C@@H:7]([CH3:38])[C:8](=[O:37])[N:9]([CH:10]3[CH2:15][CH2:14][N:13]([C:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=5[O:30][CH2:31][C@H:32]([CH3:35])[C:33]([OH:42])=[O:34])=[CH:20][C:19]=4[F:36])=[O:17])[CH2:12][CH2:11]3)[C:4]=2[CH:3]=1

Participants

8

Reactant 6

HCID 311Citric AcidHCID 1061PhosphateHCID 24437Sodium SulfiteHCID 23665760Sodium Hypochlorite2×HCID 23668197Sodium ChloriteHCID 68006276HCID 68006276, compound

Product 1

HCID 50996222HCID 50996222, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a mixed solvent solution of (3S)-7-chloro-1-{1-[(3-fluoro-2′-{[(2R)-3-hydroxy-2-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3-methyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (920 mg) in acetonitrile (10 ml) and a neutral phosphate pH standard solution (pH 6.86) (8 ml) were added at room temperature 2,2,6,6-tetramethyl-1-piperidyloxy radical (25.3 mg), 79% sodium chlorite (371 mg) and a 5% aqueous sodium hypochlorite solution (0.041 ml). After the reaction solution was stirred at 50° C. overnight, 2,2,6,6-tetramethyl-1-piperidyloxy radical (25.3 mg) and a 5% aqueous sodium hypochlorite solution (0.041 ml) were added, and further stirred for 4 hours. The reaction solution was brought back to room temperature, and an aqueous sodium sulfite solution and a 10% aqueous citric acid solution were added, and extracted with dichloromethane. The organic layer was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford (2S)-3-{[4′-({4-[(3S)-7-chloro-3-methyl-2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl]piperidin-1-yl}carbonyl)-3′-fluorobiphenyl-2-yl]oxy}-2-methylpropanoic acid (701 mg).

Workup

  1. stirringfurther stirred for 4 hours
  2. customwas brought back to room temperature
  3. extractionextracted with dichloromethane
  4. washThe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-99d63bdff33e43ab87e98f5abb7f4566
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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