Potassium Carbonate → 5-(3-Methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[3.3.1]nonane oxalate salt

HRID 1073839Notes

Reaction equation

HRID 1073839 reaction equation
Cl.[N:2]12[CH2:10][C:6]([C:11]([OH:13])=[O:12])([CH2:7][CH2:8][CH2:9]1)[CH2:5][CH2:4][CH2:3]2.S(Cl)(Cl)=O.[C:18](=[N:21][OH:22])([NH2:20])[CH3:19].[C:23](=[O:26])([O-:25])[O-].[K+].[K+]>C(Cl)(Cl)Cl.O.C1(C)C(C)=CC=CC=1>[C:11]([OH:13])(=[O:12])[C:23]([OH:25])=[O:26].[CH3:19][C:18]1[N:20]=[C:11]([C:6]23[CH2:10][N:2]([CH2:9][CH2:8][CH2:7]2)[CH2:3][CH2:4][CH2:5]3)[O:22][N:21]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 30926N-HydroxyacetamidineHCID 677598761-Azabicyclo[3.3.1]nonane-5-carboxylic acid hydrochloride

Product 1

HCID 198876135-(3-Methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[3.3.1]nonane oxalate saltYield 89%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 7237O-XyleneSolvent

Procedure

1-Azabicyclo[3.3.1]non-5-ylcarboxylic acid hydrochloride salt (D14) (1.79 g, 0.0087 mole) was treated with thionyl chloride (20 ml) and heated under reflux for 5 h. The solution was concentrated in vacuo to leave a white solid, which was taken up in chloroform (150 ml), treated with acetamide oxime (D17) (770mg, 0.0104 mole) and heated under reflux for 6 h. The reaction mixture was basified with saturated potassium carbonate solution and extracted with chloroform (3×80 ml). The combined extracts were dried (Na2SO4) and concentrated to leave a white solid, which was treated with xylene (200 ml) and heated under reflux for 1.5 h, using a Dean and Stark head to trap water formed. The reaction mixture was concentrated in vacuo to leave a yellow oil, which was chromatographed on silica gel eluting with 5% methanol/chloroform to give a colourless oil (1.60 g, 89%). This was converted to the oxalate salt and recrystallised from ethanol/ether to give the title compound (E9) as a white solid m.p. 168°-170° C.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 5 h
  3. concentrationThe solution was concentrated in vacuo
  4. customto leave a white solid, which
  5. temperatureheated
  6. temperatureunder reflux for 6 h
  7. extractionextracted with chloroform (3×80 ml)
  8. dry with materialThe combined extracts were dried (Na2SO4)
  9. concentrationconcentrated
  10. customto leave a white solid, which
  11. temperatureheated
  12. temperatureunder reflux for 1.5 h
  13. customformed
  14. concentrationThe reaction mixture was concentrated in vacuo
  15. customto leave a yellow oil, which
  16. customwas chromatographed on silica gel eluting with 5% methanol/chloroform

Sources & evidence

ORD record
ord-5e7637d6bec74a6a83a151918b1972a3
Source dataset
uspto-grants-1990_11
Patent number
US04971975

Reaction notes

Loading…