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

HRID 388492Notes

Reaction equation

HRID 388492 reaction equation
Cl.[CH2:2]([O:9][C:10]([NH:12][C:13]1[CH:33]=[CH:32][C:16]([O:17][C:18]2[CH:23]=[CH:22][N:21]=[C:20]([NH:24]C(=O)OC(C)(C)C)[CH:19]=2)=[CH:15][C:14]=1[F:34])=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>C(OCC)(=O)C>[NH2:24][C:20]1[CH:19]=[C:18]([O:17][C:16]2[CH:32]=[CH:33][C:13]([NH:12][C:10](=[O:11])[O:9][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)=[C:14]([F:34])[CH:15]=2)[CH:23]=[CH:22][N:21]=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 solution (120 ml) was cooled in an ice bath. To this was added tert-butyl [4-(4-benzyloxycarbonylamino-3-fluorophenoxy)pyridin-2-yl]carbamate (3.92 g) while stirring and the mixture was further stirred for 10 minutes in an ice bath. The reaction mixture was then further stirred for 3.5 hours at room temperature. The reaction mixture was concentrated under reduced pressure. Ethyl acetate (150 ml) and a saturated aqueous solution of sodium hydrogencarbonate (70 ml) were then added and partitioned. The aqueous layer was extracted with ethyl acetate (50 ml). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. The dried organic layer was concentrated under reduced pressure. The obtained crystals were suspended in a mixed solvent of hexane and ethyl acetate (5:1). The crystals were collected by filtration and washed with a mixed solvent of hexane and ethyl acetate (5:1). The crystals were then suction-dried at room temperature to give the title compound as pale yellow crystals (2.93 g, 95.9%).

Workup

  1. stirringthe mixture was further stirred for 10 minutes in an ice bath
  2. stirringThe reaction mixture was then further stirred for 3.5 hours at room temperature
  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 then added
  5. custompartitioned
  6. extractionThe aqueous layer was extracted with ethyl acetate (50 ml)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationThe dried organic layer was concentrated under reduced pressure
  10. filtrationThe crystals were collected by filtration
  11. washwashed with a mixed solvent of hexane and ethyl acetate (5:1)
  12. customThe crystals were then suction-dried at room temperature

Sources & evidence

ORD record
ord-cc3ae84858064ef495d291fa6d97c920
Source dataset
uspto-grants-2013_02
Patent number
US08377938B2

Reaction notes

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