Water → HCID 58494654, compound

HRID 516231Notes

Reaction equation

HRID 516231 reaction equation
[OH:1][C:2]1[C:19]([NH:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:18][C:5]2[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][CH2:10][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:34][C:35](OC)=[O:36].O>CN(C=O)C>[O:36]=[C:35]1[CH2:34][O:1][C:2]2[C:19](=[CH:18][C:5]3[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][CH2:10][C:4]=3[CH:3]=2)[N:20]1[CH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 58495397HCID 58495397, compound

Product 1

HCID 58494654HCID 58494654, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 215 mg of t-butyl 7-hydroxy-8-(tetrahydro-2H-pyran-4-ylamino)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate in 4 ml of DMF were added 98 mg of potassium carbonate and 0.062 ml of methyl bromoacetate, followed by stirring at room temperature for 6 hours. To the reaction mixture was added water, followed by extraction with EtOAc twice. The combined organic layer was washed with saturated brine three times, dried over anhydrous sodium sulfate, and then filtered, and the solvent was evaporated under reduced pressure. To a solution of 259 mg of the resulting residue in 7 ml of EtOH was added 1.2 ml of a 1 M aqueous sodium hydroxide solution, followed by stirring at 50° C. overnight. Further, 1.2 ml of a 1 M aqueous hydrochloric acid solution was added thereto under ice-cooling, followed by extraction with chloroform twice, and the combined organic layer was dried over anhydrous sodium sulfate and then filtered. The solvent was evaporated under reduced pressure. To a solution of 239 mg of the resulting residue in 4 ml of DMF were added 120 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 84 mg of HOBt at room temperature, followed by stirring at room temperature overnight. Water was added thereto, followed by extraction with EtOAc twice. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc) to obtain 153 mg of t-butyl 3-oxo-4-(tetrahydro-2H-pyran-4-yl)-3,4,6,7,9,10-hexahydro[1,4]oxazino[2,3-h][3]benzazepine-8(2H)-carboxylate as a white solid.

Workup

  1. extractionfollowed by extraction with EtOAc twice
  2. washThe combined organic layer was washed with saturated brine three times
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. additionTo a solution of 259 mg of the resulting residue in 7 ml of EtOH was added 1.2 ml of a 1 M aqueous sodium hydroxide solution
  7. stirringby stirring at 50° C. overnight
  8. additionFurther, 1.2 ml of a 1 M aqueous hydrochloric acid solution was added
  9. temperatureunder ice-cooling
  10. extractionfollowed by extraction with chloroform twice
  11. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. customThe solvent was evaporated under reduced pressure
  14. additionTo a solution of 239 mg of the resulting residue in 4 ml of DMF were added 120 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 84 mg of HOBt at room temperature
  15. stirringby stirring at room temperature overnight
  16. additionWater was added
  17. extractionfollowed by extraction with EtOAc twice
  18. washThe combined organic layer was washed with saturated brine
  19. dry with materialdried over anhydrous sodium sulfate
  20. filtrationfiltered
  21. customthe solvent was evaporated under reduced pressure
  22. customThe residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc)

Sources & evidence

ORD record
ord-24985d31b09c452c94be9e2f3d0a6e94
Source dataset
uspto-grants-2015_08
Patent number
US09108977B2

Reaction notes

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