HCID 18319805, compound → HCID 46193106, compound

HRID 1699414Notes

Reaction equation

HRID 1699414 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([NH:10][C:11]1[CH:27]=[CH:26][C:14]([O:15][CH2:16][CH2:17][NH:18][C:19](=O)OC(C)(C)C)=[CH:13][CH:12]=1)=[O:9].[ClH:28].C([O:32][CH2:33][CH3:34])(=O)C>CO>[ClH:28].[OH:32][C@H:33]([C:34]1[CH:8]=[CH:7][CH:2]=[CH:3][CH:4]=1)[CH2:19][NH:18][CH2:17][CH2:16][O:15][C:14]1[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[CH2:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[CH:27][CH:26]=1

Participants

4

Reactant 2

HCID 18319805HCID 18319805, compoundHCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 46193106HCID 46193106, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3.62 g of tert-butyl N-[2-[4-[[2-(2-pyridyl)acetyl]amino]phenoxy]ethyl]carbamate in 30 ml of methanol was added 50 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 40 ml of methanol, and 1.02 g of (R)-styrene oxide was added thereto. After the reaction solution was heated to reflux for 26 hours, the solvent was evaporated in vacuo. The resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1→10/1) and dissolved in methanol, 0.59 ml of a 4N hydrogen chloride-ethyl acetate solution was added, and the solvent was evaporated in vacuo. The resulting crude crystals were recrystallized from methanol-ethanol to give 320 mg of (R)-4′-[2-[(2-hydroxy-2-phenylethyl)-amino]ethoxy]-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 40 ml of methanol
  7. addition1.02 g of (R)-styrene oxide was added
  8. temperatureAfter the reaction solution was heated
  9. temperatureto reflux for 26 hours
  10. customthe solvent was evaporated in vacuo
  11. customThe resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1→10/1)
  12. dissolutiondissolved in methanol
  13. addition0.59 ml of a 4N hydrogen chloride-ethyl acetate solution was added
  14. customthe solvent was evaporated in vacuo
  15. customThe resulting crude crystals were recrystallized from methanol-ethanol

Sources & evidence

ORD record
ord-481d1ccc545e416690544ab02f0b51c7
Source dataset
uspto-grants-2002_02
Patent number
US06346532B1

Reaction notes

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