Citric Acid → HCID 68005991, compound

HRID 1026597Notes

Reaction equation

HRID 1026597 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[O:24][C@H:25]([CH3:29])[CH2:26][CH2:27][OH:28])[CH:5]=[CH:6][C:7]=1[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9].P([O-])([O-])([O-])=O.Cl([O-])=O.[Na+].Cl[O-:40].[Na+].S([O-])([O-])=O.[Na+].[Na+].C(O)(=O)[CH2:49][C:50]([CH2:55]C(O)=O)([C:52](O)=O)O>C(#N)C>[C:50]([O:28][C:27](=[O:40])[CH2:26][C@H:25]([O:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:4]1[CH:5]=[CH:6][C:7]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])=[C:2]([F:1])[CH:3]=1)[CH3:29])([CH3:55])([CH3:52])[CH3:49]

Participants

8

Reactant 6

HCID 311Citric AcidHCID 1061PhosphateHCID 24437Sodium SulfiteHCID 23665760Sodium HypochloriteHCID 23668197Sodium ChloriteHCID 68006156HCID 68006156, compound

Product 1

HCID 68005991HCID 68005991, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a mixed solvent solution of benzyl 3-fluoro-2′-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-carboxylate (13.4 g) in acetonitrile (252 ml) and a neutral phosphate pH standard solution (pH 6.86) (198 ml) were added at room temperature a 2,2,6,6-tetramethyl-1-piperidyloxy radical (533 mg), 79% sodium chlorite (7.83 g) and a 5% aqueous sodium hypochlorite solution (2.0 ml). The reaction solution was stirred at 50° C. for 4.5 hours. After the reaction solution was cooled to room temperature, 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. To a toluene solution (80 ml) of the resulting residue (11.0 g) was added at room temperature a supernatant (34 ml) containing tert-butyl N,N′-diisopropylimidocarbamate prepared in the method described in Example 1-1, followed by stirring at 60° C. for 4.5 hours. The reaction solution was poured into ice water, and then filtered through Celite. After the filtrate was separated, the aqueous layer was extracted with ethyl acetate. The collected 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 benzyl 2′-{[(1R)-3-tert-butoxy-1-methyl-3-oxopropyl]oxy}-3-fluorobiphenyl-4-carboxylate (12.8 g).

Workup

  1. temperatureAfter the reaction solution was cooled to room temperature
  2. extractionextracted with dichloromethane
  3. washThe organic layer was washed with saturated sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. additionTo a toluene solution (80 ml) of the resulting residue (11.0 g) was added at room temperature a supernatant (34 ml)
  7. additioncontaining tert-butyl N,N′-diisopropylimidocarbamate
  8. customprepared in the method
  9. stirringby stirring at 60° C. for 4.5 hours
  10. filtrationfiltered through Celite
  11. customAfter the filtrate was separated
  12. extractionthe aqueous layer was extracted with ethyl acetate
  13. washThe collected organic layer was washed with saturated sodium chloride solution
  14. dry with materialdried over anhydrous sodium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-480e30fe4a1b4cc2a03371f148f21076
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

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