Sodium Hydroxide → 3-methoxy-N-{1-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)methyl]piperidin-4-yl}benzamide

HRID 1256279Notes

Reaction equation

HRID 1256279 reaction equation
[O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([CH:12]=O)=[CH:7][CH:8]=2)[NH:3]1.[CH3:14][O:15][C:16]1[CH:17]=[C:18]([CH:28]=[CH:29][CH:30]=1)[C:19]([NH:21][CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:20].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>C(Cl)(Cl)Cl.CCOC(C)=O.O.CC(O)=O>[CH3:14][O:15][C:16]1[CH:17]=[C:18]([CH:28]=[CH:29][CH:30]=1)[C:19]([NH:21][CH:22]1[CH2:27][CH2:26][N:25]([CH2:12][C:6]2[CH:5]=[C:4]3[C:9]([CH2:10][CH2:11][C:2](=[O:1])[NH:3]3)=[CH:8][CH:7]=2)[CH2:24][CH2:23]1)=[O:20]

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 14451573-methoxy-N-piperidin-4-ylbenzamideHCID 5049666Sodium triacetoxyborohydrideHCID 593980391,2,3,4-Tetrahydro-2-oxo-7-quinolinecarboxaldehyde

Product 1

HCID 452557883-methoxy-N-{1-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)methyl]piperidin-4-yl}benzamideYield 75.5%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Step R1-5: To a suspension of 2-oxo-1,2,3,4-tetrahydroquinoline-7-carbaldehyde (135 g) in CHCl3 (1.4 L) were added 3-methoxy-N-(piperidin-4-yl)benzamide (190 g) and AcOH (45 mL) at room temperature. The mixture was stirred at room temperature for 2 hours. After cooling to 0° C., NaBH(OAc)3 was added portionwise. The mixture was stirred at room temperature for 19 hours. After cooling to 0° C., 8 M aqueous NaOH (0.5 L) and water (0.5 L) were added to the reaction mixture. The organic layer was separated, washed with water and brine, dried over MgSO4 and concentrated to obtain a colorless solid. The solid was suspended in EtOAc (3.0 L) and the mixture was refluxed for 1 hour and cooled to room temperature. The precipitate was filtrated to obtain a colorless solid. The solid was suspended again in EtOAc (2.4 L), and the mixture was refluxed for 1 hour and cooled to room temperature. The precipitate was filtrated to obtain the titled compound as a colorless solid (229 g).

Workup

  1. temperatureAfter cooling to 0° C.
  2. stirringThe mixture was stirred at room temperature for 19 hours
  3. temperatureAfter cooling to 0° C.
  4. customThe organic layer was separated
  5. washwashed with water and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customto obtain a colorless solid
  9. temperaturethe mixture was refluxed for 1 hour
  10. temperaturecooled to room temperature
  11. filtrationThe precipitate was filtrated
  12. customto obtain a colorless solid
  13. temperaturethe mixture was refluxed for 1 hour
  14. temperaturecooled to room temperature
  15. filtrationThe precipitate was filtrated

Sources & evidence

ORD record
ord-86ff23cddb8f449d8ed8003138a10d37
Source dataset
uspto-grants-2013_06
Patent number
US08461182B2

Reaction notes

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