Sodium Hydroxide → 7-Phenyl-1-azabicyclo[4.2.0]octan-8-one

HRID 891227Notes

Reaction equation

HRID 891227 reaction equation
[OH-].[Na+].C1(C)C=CC(S(NN=[C:14]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:15]([N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:16])(=O)=O)=CC=1>[Cl-].C([N+](CCCCCCCC)(CCCCCCCC)C)CCCCCCC.C1(C)C=CC=CC=1>[C:23]1([CH:14]2[C:15](=[O:16])[N:17]3[CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22]3)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 85395106Methylphenidate Hydrochloride Impurity 16

Product 1

HCID 123162767-Phenyl-1-azabicyclo[4.2.0]octan-8-oneYield 102.8%

Reagents, catalysts & solvents 2

HCID 21218Trioctylmethylammonium chlorideCatalystHCID 1140TolueneSolvent

Procedure

Sodium hydroxide, 50% aqueous solution (1.09 Kg, 13.6 mol, 1.05 eq) was added to a stirred mixture of 1-(phenylglyoxylyl)piperidine p-toluenesulfonylhydrazone (5.00 Kg, 13.0 mol, 1 eq), phase transfer catalyst (PTC) trioctylmethylammonium chloride (aliquat 336) (60.0 g, 0.15 mol, 0.01 eq) and toluene (50 L) at 20–30° C. The mixture was heated to reflux and monitored by both TLC and the color of the reaction mixture. The originally yellow solution in 10 minutes turned bright orange as the diazo compound was formed. After 6.5 hours at reflux, the solution re-assumed a yellow color and TLC indicated that no starting material was present. Crushed ice (20 Kg) was added to the reaction mixture (temperature of the mixture was dropped to 15° C.). The organic layer was separated, washed with brine (15 L) and evaporated under reduced pressure to give 2.69 Kg (quantitative yield) of 7-phenyl-1-azabicyclo [4.2.0]octan-8-one with R*R*/S*R* 3.3:1 by GC.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. customwas formed
  4. temperatureAfter 6.5 hours at reflux
  5. additionwas dropped to 15° C.)
  6. customThe organic layer was separated
  7. washwashed with brine (15 L)
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-96c829ef8e9c4d30909ed6480e69e278
Source dataset
uspto-grants-2006_02
Patent number
US07002016B2

Reaction notes

Loading…