Hydrogen chloride-ethyl acetate → HCID 178475075, compound

HRID 2368153Notes

Reaction equation

HRID 2368153 reaction equation
[CH:1]1([CH2:4][CH2:5][O:6][C:7]2[CH:8]=[CH:9][C:10]3[C:14]([CH:15]=2)=[N:13][N:12]([C@H:16]2[CH2:21][CH2:20][C@H:19]([O:22][CH2:23][C@@H:24]([NH:26][C:27](=[O:33])OC(C)(C)C)[CH3:25])[CH2:18][CH2:17]2)[CH:11]=3)[CH2:3][CH2:2]1.Cl.[C:35](OCC)(=O)C>C(OCC)(=O)C>[CH:1]1([CH2:4][CH2:5][O:6][C:7]2[CH:8]=[CH:9][C:10]3[C:14]([CH:15]=2)=[N:13][N:12]([C@H:16]2[CH2:21][CH2:20][C@H:19]([O:22][CH2:23][C@@H:24]([NH:26][C:27](=[O:33])[CH3:35])[CH3:25])[CH2:18][CH2:17]2)[CH:11]=3)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 178461790HCID 178461790, compound

Product 1

HCID 178475075HCID 178475075, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl [(1S)-2-({trans-4-[6-(2-cyclopropylethoxy)-2H-indazol-2-yl]cyclohexyl}oxy)-1-methylethyl]carbamate (1.2 g) in ethyl acetate (30 mL) was added 4M hydrogen chloride/ethyl acetate (10 mL), and the mixture was stirred at room temperature for 5 hr. The reaction mixture was concentrated under reduced pressure, the obtained residue was dissolved in pyridine (10 mL), and acetic anhydride (1 mL) was added thereto at room temperature. The reaction mixture was stirred at room temperature for 3 hr, and concentrated under reduced pressure. The obtained residue was dissolved in ethyl acetate and water, and the solution was extracted with ethyl acetate. The organic layer was washed successively with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was separated by HPLC (C18, mobile phase: ammonium hydrogen carbonate aqueous solution/acetonitrile), and water was added to the obtained fraction. The mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (153 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe obtained residue was dissolved in pyridine (10 mL)
  3. additionacetic anhydride (1 mL) was added
  4. customat room temperature
  5. stirringThe reaction mixture was stirred at room temperature for 3 hr
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe obtained residue was dissolved in ethyl acetate
  8. extractionwater, and the solution was extracted with ethyl acetate
  9. washThe organic layer was washed successively with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe obtained residue was separated by HPLC (C18, mobile phase: ammonium hydrogen carbonate aqueous solution/acetonitrile), and water
  13. additionwas added to the obtained fraction
  14. extractionThe mixture was extracted with ethyl acetate
  15. dry with materialdried over anhydrous magnesium sulfate
  16. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1073e82bd25a4b8f9446ccb2a7960882
Source dataset
uspto-grants-2014_04
Patent number
US08703758B2

Reaction notes

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