Hydrochloric Acid → 4-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridine-2-carboxylic acid

HRID 2265601Notes

Reaction equation

HRID 2265601 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])=[CH:14][C:13]=2[F:29])[CH:8]=[CH:7][N:6]=1)=[O:4].O.[OH-].[Li+].Cl>CO.CN(C)C=O>[CH2:22]([O:21][C:19]([NH:18][C:15]1[CH:16]=[CH:17][C:12]([O:11][C:9]2[CH:8]=[CH:7][N:6]=[C:5]([C:3]([OH:4])=[O:2])[CH:10]=2)=[C:13]([F:29])[CH:14]=1)=[O:20])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 576777514-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridine-2-carboxylic acid methyl ester

Product 1

HCID 231529624-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridine-2-carboxylic acidYield 92.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

4-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridine-2-carboxylic acid methyl ester (10.7 g) was dissolved in methanol (450 ml) and N,N-dimethylformamide (150 ml), and water (75 ml) and lithium hydroxide (1.36 g) were added thereto, followed by stirring at room temperature for 1 hr. 1N hydrochloric acid (100 ml) was added thereto, then the reaction mixture was concentrated under reduced pressure and liquid-liquid separation was carried out after addition of ethyl acetate (500 ml), and the precipitated solid was collected by filtration. The resultant solid was washed with water and hexane, and dried under aeration. The organic layer of the filtrate obtained above was washed with water (100 ml×2) and brine (200 ml) and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the resultant solid was washed with water and hexane and dried under aeration. This solid was combined with the solid obtained above, and dried at 60° C. overnight to provide the titled compound as white powder (9.53 g, 92.3%).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure and liquid-liquid separation
  2. additionafter addition of ethyl acetate (500 ml)
  3. filtrationthe precipitated solid was collected by filtration
  4. washThe resultant solid was washed with water and hexane
  5. customdried under aeration
  6. customThe organic layer of the filtrate obtained
  7. washabove was washed with water (100 ml×2) and brine (200 ml)
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was removed under reduced pressure
  10. washthe resultant solid was washed with water and hexane
  11. customdried under aeration
  12. customobtained above, and
  13. customdried at 60° C. overnight

Sources & evidence

ORD record
ord-f32640f267e647d49036ec3b4dccca69
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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