Potassium Hydroxide → 2-[3-(4-Chlorophenyl)propyl]-1-azabicyclo[2.2.2]octane

HRID 745557Notes

Reaction equation

HRID 745557 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH2:10][CH2:11][CH:12]2[C:17](=O)[CH:16]3[CH2:19][CH2:20][N:13]2[CH2:14][CH2:15]3)=[CH:5][CH:4]=1.O.NN.[OH-].[K+]>C(O)COCCO>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:11][CH:12]2[CH2:17][CH:16]3[CH2:15][CH2:14][N:13]2[CH2:20][CH2:19]3)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 139715282-[3-(4-Chlorophenyl)-3-oxopropyl]-1-azabicyclo[2.2.2]octan-3-one hydrochloride

Product 1

HCID 139715122-[3-(4-Chlorophenyl)propyl]-1-azabicyclo[2.2.2]octane

Reagents, catalysts & solvents 1

HCID 8117Diethylene GlycolSolvent

Procedure

Combine 15.06 g (0.046 mole) 2-[3-(4-chlorophenyl)-3-oxopropyl]-1-azabicyclo[2.2.2]octane-3-one hydrochloride, 45 ml (0.93 mole) hydrazine monohydrate, 50.6 g (0.9 mole) potassium hydroxide and 75 ml diethylene glycol and heat to 100° C. After 3 hours, fit the reaction flask with a distillation head and heat reaction in an oil bath until oil bath temperature reaches approximately 190° C. Heat at this temperature for 5 hours. Cool the reaction mixture to room temperature. Quench the cool mixture with 500 ml H2O. Adjust the pH with concentrated hydrochloric acid to pH=1. Wash the aqueous layer 1×250 ml diethyl ether. Adjust pH of the aqueous layer to pH=11 with ammonium hydroxide. Extract with 3×250 ml methylene cloride. Dry the extracts over potassium carbonate, filter and remove the solvents in vacuo to obtain 2-[3-(4-chlorophenyl)propyl]-1-azabicyclo[2.2.2]octane as an oil. Dissolve this oil in 50 ml ethanol and acidify with HCl gas. Remove the solvents in vacuo to obtain an oil. Triturate the residue in diethyl ether to obtain the title compound. Recrystallize product from 2-propanol.

Workup

  1. temperatureheat
  2. customreaction in an oil bath until oil bath temperature
  3. customreaches approximately 190° C
  4. temperatureHeat at this temperature for 5 hours
  5. customQuench the cool mixture with 500 ml H2O
  6. washWash the aqueous layer 1×250 ml diethyl ether
  7. extractionExtract with 3×250 ml methylene cloride
  8. dry with materialDry the extracts over potassium carbonate
  9. filtrationfilter
  10. customremove the solvents in vacuo

Sources & evidence

ORD record
ord-e64792a4fa154fc392445b5c8a787d26
Source dataset
uspto-grants-1986_07
Patent number
US04599344

Reaction notes

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