Hydrochloric Acid → Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate

HRID 2066173Notes

Reaction equation

HRID 2066173 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])=[C:18]([F:33])[CH:17]=2)[CH:12]=[CH:11][N:10]=1)(C)(C)C>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)=[CH:17][C:18]=1[F:33])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57677355Tert-butyl [4-(4-benzyloxycarbonylamino-3-fluorophenoxy)pyridin-2-yl]carbamate

Product 1

HCID 57470855Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamateYield 95.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A 4N solution of hydrochloric acid in ethyl acetate (120 ml) was cooled in an ice bath. tert-Butyl[4-(4-benzyloxycarbonylamino-3-fluorophenoxy)pyridin-2-yl]carbamate (3.92 g) was added thereto while stirring, followed by stirring in an ice bath for 10 min. The reaction mixture was then stirred at room temperature for 3.5 hr. The reaction mixture was concentrated under reduced pressure. Ethyl acetate (150 ml) and a saturated aqueous solution of sodium hydrogencarbonate (70 ml) were added thereto, and liquid-liquid separation was carried out. The aqueous layer was extracted with ethyl acetate (50 ml). The combined organic layer was washed with brine and dried over anhydrous sodium sulfate. The organic layer after drying was concentrated under reduced pressure. The resultant crystals were suspended in a mixed solvent of hexane-ethyl acetate (5:1). The crystals were collected by filtration and washed with a mixed solvent of hexane-ethyl acetate (5:1). The crystals were sucked to dryness at room temperature to provide the titled compound as pale yellow crystals (2.93 g, 95.9%).

Workup

  1. stirringby stirring in an ice bath for 10 min
  2. stirringThe reaction mixture was then stirred at room temperature for 3.5 hr
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionEthyl acetate (150 ml) and a saturated aqueous solution of sodium hydrogencarbonate (70 ml) were added
  5. customliquid-liquid separation
  6. extractionThe aqueous layer was extracted with ethyl acetate (50 ml)
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe organic layer after drying
  10. concentrationwas concentrated under reduced pressure
  11. filtrationThe crystals were collected by filtration
  12. washwashed with a mixed solvent of hexane-ethyl acetate (5:1)
  13. customwere sucked to dryness at room temperature

Sources & evidence

ORD record
ord-ddbde7c6a2e14aa082f711e8c778dad4
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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