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

HRID 2265603Notes

Reaction equation

HRID 2265603 reaction equation
Cl.C(OC(=O)[NH:8][C:9]1[CH:14]=[C:13]([O:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:24])=[CH:18][C:17]=2[F:33])[CH:12]=[CH:11][N:10]=1)(C)(C)C.C(OCC)C.[OH-].[Na+]>C(OCC)(=O)C>[CH2:26]([O:25][C:23](=[O:24])[NH:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][C:13]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:8])[CH:14]=2)=[C:17]([F:33])[CH:18]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 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 8857Ethyl AcetateSolvent

Procedure

To a 4N solution of hydrochloric acid in ethyl acetate (30 ml) was added [4-(4-benzyloxycarbonylamino-2-fluorophenoxy)pyridin-2-yl]carbamic acid tert-butyl ester (510 mg) while stirring in an ice water bath. The reaction mixture was allowed to warm up to room temperature, followed by stirring for 16 hr. To the reaction mixture were added diethyl ether (10 ml) and a 5N aqueous solution of sodium hydroxide (1 ml), followed by stirring for 30 min. The separated organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml), and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, 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. To the resultant residue were added diethyl ether (4 ml) and hexane (6 ml) to suspend the precipitated solid. The solid was collected by filtration and dried under aeration to provide the titled compound as pale yellow powder (46.6 mg, 11.7%).

Workup

  1. stirringby stirring for 16 hr
  2. stirringby stirring for 30 min
  3. washThe separated organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:2) and fractions
  7. additioncontaining the target compound
  8. concentrationwere concentrated under reduced pressure
  9. additionTo the resultant residue were added diethyl ether (4 ml) and hexane (6 ml)
  10. filtrationThe solid was collected by filtration
  11. customdried under aeration

Sources & evidence

ORD record
ord-ffa85007ce32435692f06982983160e3
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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