Water → HCID 70471605, compound

HRID 745545Notes

Reaction equation

HRID 745545 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]=[C:10]2[CH:15]3[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]3)[CH2:11]2)=[CH:4][CH:3]=1.[CH3:18][S:19]([Cl:22])(=[O:21])=[O:20].O.[OH-].[Na+]>C(Cl)Cl>[ClH:22].[N:12]12[CH2:13][CH2:14][CH:15]([CH2:16][CH2:17]1)[C:10](=[CH:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][S:19]([CH3:18])(=[O:21])=[O:20])=[CH:3][CH:4]=1)[CH2:11]2

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 54055583HCID 54055583, compound

Product 1

HCID 70471605HCID 70471605, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-50 °C

Procedure

To 4.57 g (0.02 mole) of 3-[2-(4-aminophenyl)ethylidene]1-azabicyclo[2.2.2]octane dissolved in 100 ml of methylene chloride, cooled to -50° C., under a nitrogen atmosphere add dropwise a solution of 2.86 g (0.025 mole) of methanesulfonyl chloride in 25 ml of methylene chloride. After the addition is complete stir the reaction for one-half hour at -50° C. then allow to warm to room temperature. Stir at room temperature for one hour. Follow the progress of the reaction by thin-layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 95:5). At the completion of the reaction add 5 ml of water to the reaction mixture then strip the methylene chloride in vacuo. Add 50 ml of 10% sodium hydroxide. Wash the mixture with three 25 ml portions of ether and one 25 ml portion of methylene chloride. Bring the aqueous base mixture to pH=8-8.5 by the addition of 5% hydrochloric acid solution. Extract the mixture with four 100 ml portions of methylene chloride. Wash the combined methylene chloride extracts with a 50 ml portion of water and then with a 50 ml portion of saturated sodium chloride solution. Dry the methylene chloride extracts over anhydrous sodium sulfate, filter and remove the solvent in vacuo to provide the title compound as the free base.

Workup

  1. additionAfter the addition
  2. customthe reaction for one-half hour at -50° C.
  3. temperatureto warm to room temperature
  4. stirringStir at room temperature for one hour
  5. customthe progress of the reaction by thin-layer chromatography on silica gel (acetonitrile:ammonium hydroxide, 95:5)
  6. washWash the mixture with three 25 ml portions of ether and one 25 ml portion of methylene chloride
  7. additionBring the aqueous base mixture to pH=8-8.5 by the addition of 5% hydrochloric acid solution
  8. extractionExtract the mixture with four 100 ml portions of methylene chloride
  9. washWash the combined methylene chloride
  10. dry with materialDry the methylene chloride
  11. filtrationfilter
  12. customremove the solvent in vacuo

Sources & evidence

ORD record
ord-e6c6a5b5720b45d889b5d18c6174068d
Source dataset
uspto-grants-1986_07
Patent number
US04599344

Reaction notes

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