Acetic Anhydride → (-)-5-[2-(5-Methyl-1,2,4-oxadiazol-3-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]octane

HRID 44461Notes

Reaction equation

HRID 44461 reaction equation
[N:1]12[CH2:8][C:5]([C:9]3[CH:10]=[CH:11][C:12]([C:15](=[NH:18])[NH:16][OH:17])=[N:13][CH:14]=3)([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH2:2]2.[C:19](OC(=O)C)(=O)[CH3:20]>N1C=CC=CC=1>[CH3:19][C:20]1[O:17][N:16]=[C:15]([C:12]2[CH:11]=[CH:10][C:9]([C:5]34[CH2:8][N:1]([CH2:7][CH2:6]3)[CH2:2][CH2:3][CH2:4]4)=[CH:14][N:13]=2)[N:18]=1

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 178513249HCID 178513249, compound

Product 1

HCID 67050047(-)-5-[2-(5-Methyl-1,2,4-oxadiazol-3-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]octaneYield 25.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

0.28 g (1.14 mmol) of (−)-5-(azabicyclo[3.2.1]oct-5-yl)-N-hydroxypyridine-2-carboximidamide, prepared in step 7.1, dissolved in 10 ml of pyridine is introduced into a 10 ml reactor. 0.1 ml (1.13 mmol) of acetic anhydride is then added and the medium is stirred at room temperature for 15 hours and then heated at 110° C. for 5 hours. The solvent is concentrated under reduced pressure and the residue is taken up in saturated aqueous sodium carbonate solution. The aqueous phase is extracted with chloroform and the combined organic phases are dried over sodium sulfate, filtered and evaporated under vacuum. The residue is purified by chromatography on a column of silica gel, eluting with a mixture of chloroform, methanol and aqueous ammonia in 96/4/0.4 proportions. 0.077 g of (−)-5-[2-(5-methyl-1,2,4-oxadiazol-3-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]octane is thus obtained, and is dissolved in 1 ml of isopropyl alcohol to add 0.05 ml of a 5.7N solution of hydrobromic acid in acetic acid. The crystals obtained are collected by filtration and dried under reduced pressure.

Workup

  1. additionis introduced into a 10 ml reactor
  2. temperatureheated at 110° C. for 5 hours
  3. concentrationThe solvent is concentrated under reduced pressure
  4. extractionThe aqueous phase is extracted with chloroform
  5. dry with materialthe combined organic phases are dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under vacuum
  8. customThe residue is purified by chromatography on a column of silica gel
  9. washeluting with a mixture of chloroform, methanol and aqueous ammonia in 96/4/0.4 proportions

Sources & evidence

ORD record
ord-973f1c3f44a147d082ca850d6adea175
Source dataset
uspto-grants-2013_09
Patent number
US08541440B2

Reaction notes

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