Hydrochloric Acid → 8-Benzyl-8-azabicyclo(3.2.1)octan-3-one

HRID 1500616Notes

Reaction equation

HRID 1500616 reaction equation
CO[CH:3]1[CH2:7][CH2:6][CH:5](OC)[O:4]1.Cl.[CH2:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH2:19]([C:26](O)=O)[C:20](CC(O)=O)=O.[OH-].[Na+].[Cl-].[Na+]>O>[CH2:11]([N:18]1[CH:6]2[CH2:5][CH2:26][CH:19]1[CH2:20][C:3](=[O:4])[CH2:7]2)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 6

HCID 313Hydrochloric Acid3×HCID 5234Sodium ChlorideHCID 7504BenzylamineHCID 14798Sodium Hydroxide2×HCID 68328Acetonedicarboxylic acidHCID 790982,5-Dimethoxytetrahydrofuran

Product 1

HCID 1198468-Benzyl-8-azabicyclo(3.2.1)octan-3-oneYield 48.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent5×

Procedure

A mixture of 2,5-dimethoxy tetrahydrofuran (20.5 g, 155.1 mmol), water (42.5 mL) and concentrated HCl (30 mL) was stirred at room temperature for about 30 minutes. To this stirring mixture was sequentially added water (62.5 mL), a premixed solution of benzylamine (17.9 mL, 162.9 mmol), water (87.5 mL) and concentrated HCl (23 mL), a premixed solution of 1,3-acetonedicarboxylic acid (25 g) and water (100 mL), and a solution of Na2HPO4 (16.5 g) in water (50 mL). The resulting mixture was adjusted to pH 4 to 5 with 40% aqueous NaOH and stirred overnight at room temperature. The mixture was acidified to pH 3 with concentrated HCl and heated to 85° C. for 3 hours. After cooling to room temperature, the mixture was basified with 20% aqueous NaOH, saturated with solid sodium chloride and extracted with dichloromethane. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated to give a dark oil which was purified by flash column chromatography. The product was eluted with 20% ethyl acetate/hexanes. Desired fractions were combined and concentrated to give the title intermediate as a yellowish oil (16.17 g).

Workup

  1. stirringstirred overnight at room temperature
  2. temperatureheated to 85° C. for 3 hours
  3. temperatureAfter cooling to room temperature
  4. extractionextracted with dichloromethane
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a dark oil which
  10. customwas purified by flash column chromatography
  11. washThe product was eluted with 20% ethyl acetate/hexanes
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-4872f8ad4453405a97f3fc07e2eea24d
Source dataset
uspto-grants-2015_12
Patent number
US09206172B2

Reaction notes

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