Sodium Hydroxide → [4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl]carbamic acid benzyl ester

HRID 492839Notes

Reaction equation

HRID 492839 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([O:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:23])=[CH:17][C:16]=2[F:32])[CH:11]=[CH:10][N:9]=1)(C)(C)C.Cl.C(OCC)(=O)C.[OH-].[Na+]>C(OCC)C>[CH2:25]([O:24][C:22](=[O:23])[NH:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][C:12]2[CH:11]=[CH:10][N:9]=[C:8]([NH2:7])[CH:13]=2)=[C:16]([F:32])[CH:17]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 21866389Hydrogen chloride-ethyl acetateHCID 57677373[4-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridin-2-yl]carbamic acid tert-butyl ester

Product 1

HCID 57677357[4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl]carbamic acid benzyl esterYield 11.7%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

[4-(4-Benzyloxycarbonylamino-2-fluorophenoxy)pyridin-2-yl]carbamic acid tert-butyl ester (510 mg) was added to a 4N hydrochloric acid-ethyl acetate (30 ml) while cooling in an ice water bath. The reaction mixture was allowed to warm to room temperature and then stirred for 16 hours. Diethyl ether (10 ml) and 5N aqueous sodium hydroxide (1 ml) were added to the reaction mixture and stirred therewith for 30 minutes. The separated organic layer was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml) and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:2) and fractions containing the target compound were concentrated under reduced pressure. Diethyl ether (4 ml) and hexane (6 ml) were added to the resultant residue to produce a suspension of the precipitated solid. After filtering the solid, it was subjected to aeration drying to provide the title compound (46.6 mg, 11.7%) as pale yellow powder.

Workup

  1. temperaturewhile cooling in an ice water bath
  2. stirringstirred
  3. waitfor 30 minutes
  4. washThe separated organic layer was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:2) and fractions
  8. additioncontaining the target compound
  9. concentrationwere concentrated under reduced pressure
  10. additionDiethyl ether (4 ml) and hexane (6 ml) were added to the resultant residue
  11. customto produce
  12. additiona suspension of the precipitated solid
  13. filtrationAfter filtering the solid, it
  14. customdrying

Sources & evidence

ORD record
ord-a4ae9d28f5ec4fca9f4f6b6e1ed876d6
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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