Hydrochloric Acid → Hydrocodone

HRID 2375508Notes

Reaction equation

HRID 2375508 reaction equation
CC(C)([O-])C.[K+].C(C1C=CC=CC=1)(=O)C1C=CC=CC=1.[CH3:21][N:22]1[C@@H:38]2[CH2:39][C:27]3[CH:28]=[CH:29][C:30]([O:41][CH3:42])=[C:31]4[O:32][C@H:33]5[C@@H:34]([OH:40])[CH2:35][CH2:36][C@@H:37]2[C@:25]5([C:26]=34)[CH2:24][CH2:23]1.Cl>C1C=CC=CC=1>[CH3:21][N:22]1[C@@H:38]2[CH2:39][C:27]3[CH:28]=[CH:29][C:30]([O:41][CH3:42])=[C:31]4[O:32][C@H:33]5[C:34]([CH2:35][CH2:36][C@@H:37]2[C@:25]5([C:26]=34)[CH2:24][CH2:23]1)=[O:40]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3102BenzophenoneHCID 5284543DihydrocodeineHCID 23665647Potassium tert-butoxide

Product 1

HCID 5284569HydrocodoneYield 62.2%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a mixture of 1.25 g (11.1 mmol) of potassium-t-butoxide in 50 mL of benzene were added 6.78 g (37 mmol) of benzophenone and 1.12 g (3.7 mmol) of dihydrocodeine, which was allowed to reflux for 2 hours. The reaction mixture turned yellow. The reaction mixture was allowed to cool to room temperature, and 50 mL of 2N HCl was added. The resulting reaction mixture was allowed to stir for 10 minutes. The organic layer was separated and extracted with 3×40 mL of 2N HCl. The organic layer was discarded, and the aqueous layer was again extracted with 3×20 mL of dichloromethane. The aqueous layer was basified with aqueous potassium hydroxide solution to pH 12 and extracted with 5×60 mL of dichloromethane. The organic layers were combined and dried over MgSO4 and filtered. The filtrate was concentrated to give 691 mg (2.3 mmol, 55%) of 3 as a yellow solid.

Workup

  1. temperatureto reflux for 2 hours
  2. customThe resulting reaction mixture
  3. customThe organic layer was separated
  4. extractionextracted with 3×40 mL of 2N HCl
  5. extractionthe aqueous layer was again extracted with 3×20 mL of dichloromethane
  6. extractionextracted with 5×60 mL of dichloromethane
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-400c1a96f9994157867ab13e3153ce1d
Source dataset
uspto-grants-2008_12
Patent number
US07465797B2

Reaction notes

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