Hydrogen chloride-ethyl acetate → HCID 67778243, compound

HRID 1026252Notes

Reaction equation

HRID 1026252 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]2[C:11]([CH:12]=1)=[N:10][N:9]([C:13]1[CH:30]=[CH:29][C:16]([O:17][CH2:18][C@@H:19]([NH:21][C:22](=O)[O:23]C(C)(C)C)[CH3:20])=[CH:15][C:14]=1[F:31])[CH:8]=2)[CH3:2].Cl.[C:33](OCC)(=O)C>C(OCC)(=O)C>[OH2:3].[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]2[C:11]([CH:12]=1)=[N:10][N:9]([C:13]1[CH:30]=[CH:29][C:16]([O:17][CH2:18][C@@H:19]([NH:21][C:22](=[O:23])[CH3:33])[CH3:20])=[CH:15][C:14]=1[F:31])[CH:8]=2)[CH3:2]

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 86666276HCID 86666276, compound

Product 1

HCID 67778243HCID 67778243, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl {(1S)-2-[4-(6-ethoxy-2H-indazol-2-yl)-3-fluorophenoxy]-1-methylethyl}carbamate (6.53 g), 4M hydrogen chloride/ethyl acetate (20 mL) and ethyl acetate (40 mL) was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the obtained residue was mixed with acetic anhydride (20 mL) and pyridine (50 mL). The obtained mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with THF and ethyl acetate, and the mixture was washed three times with 1M hydrochloric acid. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in ethanol, and the solution was filtered through silica gel. The filtrate was concentrated, and the residue was recrystallized (ethanol/ethyl acetate) to give the title compound as colorless crystals (2.36 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe obtained residue was mixed with acetic anhydride (20 mL) and pyridine (50 mL)
  3. stirringThe obtained mixture was stirred at room temperature for 1 hr
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. additionthe residue was diluted with THF and ethyl acetate
  6. washthe mixture was washed three times with 1M hydrochloric acid
  7. extractionThe separated aqueous layer was extracted again with ethyl acetate
  8. washThe combined organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. dissolutionThe residue was dissolved in ethanol
  12. filtrationthe solution was filtered through silica gel
  13. concentrationThe filtrate was concentrated
  14. customthe residue was recrystallized (ethanol/ethyl acetate)

Sources & evidence

ORD record
ord-1072416629884af380a740d10d680ccd
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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