HCID 18319680, compound → HCID 46192146, compound

HRID 1699415Notes

Reaction equation

HRID 1699415 reaction equation
[CH3:1][C:2]([NH:21][C:22](=O)OC(C)(C)C)([CH3:20])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:19])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:6][CH:5]=1.[ClH:29].C([O:33][CH2:34][CH3:35])(=O)C>CO>[ClH:29].[CH3:20][C:2]([CH3:1])([NH:21][CH2:22][C@H:34]([OH:33])[C:35]1[CH:5]=[CH:4][CH:3]=[CH:2][CH:1]=1)[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11](=[O:19])[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 18319680HCID 18319680, compoundHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 46192146HCID 46192146, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 490 mg of tert-butyl N-[1,1-di-methyl-2-[4-[[2-(2-pyridyl)acetyl]amino]phenyl]ethyl]-carbamate in 10 ml of methanol was added 30 ml of a 4N hydrochloride-ethyl acetate solution. After the reaction solution was stirred at room temperature for eight hours, the solvent was evaporated in vacuo. To the residue were added an aqueous solution of sodium hydrogen carbonate and potassium carbonate to adjust to pH about 12. The resulting aqueous phase was extracted with a mixed solvent of chloroform and tetrahydrofuran. The organic layer was dried over anhydrous magnesium sulfate and concentrated, the resulting residue was dissolved in 2 ml of 2-propanol and 2 ml of methanol, and 120 mg of (R)-styrene oxide was added thereto. After the reaction solution was heated to reflux for 24 hours, the solvent was evaporated in vacuo. The resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1→15/1) and dissolved in methanol, 0.1 ml of a 4N hydrogen chloride-ethyl acetate solution was added, and the solvent was evaporated in vacuo. The resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=5/1) and a reversed phase column chromatography (eluent: water/methanol=2/1→1/1) to give 35 mg of (R)-4′-[2,2-dimethyl-2-[(2-hydroxy-2-phenylethyl)amino]ethyl]-2-(2-pyridyl)acetanilide hydrochloride.

Workup

  1. customthe solvent was evaporated in vacuo
  2. additionTo the residue were added an aqueous solution of sodium hydrogen carbonate and potassium carbonate
  3. extractionThe resulting aqueous phase was extracted with a mixed solvent of chloroform and tetrahydrofuran
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. dissolutionthe resulting residue was dissolved in 2 ml of 2-propanol
  7. addition2 ml of methanol, and 120 mg of (R)-styrene oxide was added
  8. temperatureAfter the reaction solution was heated
  9. temperatureto reflux for 24 hours
  10. customthe solvent was evaporated in vacuo
  11. customThe resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1→15/1)
  12. dissolutiondissolved in methanol
  13. addition0.1 ml of a 4N hydrogen chloride-ethyl acetate solution was added
  14. customthe solvent was evaporated in vacuo
  15. customThe resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=5/1)

Sources & evidence

ORD record
ord-07f4e9fa88e84a77ad8f6692190f5151
Source dataset
uspto-grants-2002_02
Patent number
US06346532B1

Reaction notes

Loading…