Sodium Carbonate → Ethyl 4-(4-(benzyloxycarbonylamino)piperidin-1-yl)benzoate

HRID 710556Notes

Reaction equation

HRID 710556 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8](F)=[CH:7][CH:6]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].[NH2:19][CH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:32]([O:39][C:40](Cl)=[O:41])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CS(C)=O.C1COCC1.O>[CH2:32]([O:39][C:40]([NH:19][CH:20]1[CH2:25][CH2:24][N:23]([C:8]2[CH:9]=[CH:10][C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:12])=[CH:6][CH:7]=2)[CH2:22][CH2:21]1)=[O:41])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 67976Benzoic acid, 4-fluoro-, ethyl esterHCID 4243614-Piperidinamine

Product 1

HCID 66691942Ethyl 4-(4-(benzyloxycarbonylamino)piperidin-1-yl)benzoateYield 74%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

4-Fluorobenzoic acid ethyl ester (25.0 g, 149 mmol) was dissolved in dimethyl sulfoxide (hereinafter referred to as DMSO) (100 mL), and potassium carbonate (31.0 g, 224 mmol) and 4-aminopiperidine (18.8 mL, 177 mmol) were added thereto, followed by stirring at 130° C. for 20 hours. After the reaction mixture was cooled to room temperature, water was added to the mixture and the precipitate was collected by filtration, thereby giving ethyl 4-(4-aminopiperidin-1-yl)benzoate (36.0 g, 98%) as a yellow solid. This amino compound (15.7 g, 63.2 mmol) was dissolved in THF (200 mL), and a 2N sodium carbonate aqueous solution (63 mL) was added thereto. Subsequently, benzyloxycarbonyl chloride (11.7 mL, 82.2 mmol) was added to the mixture, followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride aqueous solution, and then dried over anhydrous sodium sulfate. After the desiccant was filtered off, the solvent was evaporated under reduced pressure to precipitate a solid, which was collected by filtration and dried under reduced pressure, thereby giving the title compound (18.0 g, 74%) as a white solid.

Workup

  1. additionwere added
  2. temperatureAfter the reaction mixture was cooled to room temperature
  3. filtrationthe precipitate was collected by filtration
  4. stirringby stirring at room temperature for 2 hours
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe organic layer was washed with water
  7. dry with materiala saturated sodium chloride aqueous solution, and then dried over anhydrous sodium sulfate
  8. filtrationAfter the desiccant was filtered off
  9. customthe solvent was evaporated under reduced pressure
  10. customto precipitate a solid, which
  11. filtrationwas collected by filtration
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-ae56099a8b6d49de9dbe73d67bd5ec99
Source dataset
uspto-grants-2015_11
Patent number
US09181183B2

Reaction notes

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