Triethylamine → Oxothien-2-yl-acetic Acid 1-azabicyclo[2.2.2]oct-4-yl Ester

HRID 522461Notes

Reaction equation

HRID 522461 reaction equation
C(Cl)(=O)C(Cl)=O.[O:7]=[C:8]([C:12]1[S:13][CH:14]=[CH:15][CH:16]=1)[C:9]([OH:11])=[O:10].O[C:18]12[CH2:25][CH2:24][N:21]([CH2:22][CH2:23]1)[CH2:20][CH2:19]2.C(N(CC)CC)C>CN(C)C=O.C(Cl)(Cl)Cl>[N:21]12[CH2:24][CH2:25][C:18]([O:10][C:9](=[O:11])[C:8](=[O:7])[C:12]3[S:13][CH:14]=[CH:15][CH:16]=3)([CH2:23][CH2:22]1)[CH2:19][CH2:20]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 776942-Thiopheneglyoxylic acidHCID 1412901-Azabicyclo(2.2.2)octan-4-ol

Product 1

HCID 66592495Oxothien-2-yl-acetic Acid 1-azabicyclo[2.2.2]oct-4-yl Ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6212ChloroformSolvent2×

Procedure

Oxalyl chloride (1.5 ml,0.017 mol) was added to a solution of oxothien-2-yl-acetic acid (2.24 g, 0,014 mol) and dimethylformamide (one drop) in 30 ml of chloroform (etanol free) at 0° C. The mixture was stirred and allowed to warm at room temperature. After one hour the solvent was evaporated. The residue was dissolved in chloroform and evaporated again. This procedure was repeated two times. The product obtained was disolved in CHCl3 (30 ml) and added to a suspension of 1.1 g (0,009 mols) of 4-hydroxy-1-azabicyclo[2.2.2]octane, 1.8 ml of triethylamine (0.013 mols), 0.6 g (0.9 mmols) of N-(methylpolystyrene)-4-(methylamino)pyridine at 70° C. The mixture was refluxed for 1 hour, cooled, filtered and washed with water. The title product was extracted with a solution of diluted HCl, washed with CHCl3, basified with K2CO3 and extracted again with CHCl3. After removal of the solvent 1.47 g (45%) of a solid was obtained. 1H-NMR (dmso): δ 2.0 (m, 6H), 2.9 (m,6H), 7.35 (m, 1H), 8.05 (m, 1H), 8.3 (m, 1H).

Workup

  1. customAfter one hour the solvent was evaporated
  2. dissolutionThe residue was dissolved in chloroform
  3. customevaporated again
  4. customThe product obtained
  5. temperatureThe mixture was refluxed for 1 hour
  6. temperaturecooled
  7. filtrationfiltered
  8. washwashed with water
  9. extractionThe title product was extracted with a solution of diluted HCl
  10. washwashed with CHCl3
  11. extractionextracted again with CHCl3
  12. customAfter removal of the solvent 1.47 g (45%) of a solid
  13. customwas obtained

Sources & evidence

ORD record
ord-2ca0a0ca7f354076abfd6ea8fe01a13e
Source dataset
uspto-grants-2016_05
Patent number
US09333195B2

Reaction notes

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