Chloride → Ethyl nipecotate

HRID 1417036Notes

Reaction equation

HRID 1417036 reaction equation
[Cl-].C([C@@H]([C@H](C(O)=O)O)O)(O)=O.[CH2:12]([O:14][C:15]([C@@H:17]1[CH2:22][CH2:21][CH2:20][NH:19][CH2:18]1)=[O:16])[CH3:13].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CC(=O)CC>[CH2:12]([O:14][C:15]([CH:17]1[CH2:22][CH2:21][CH2:20][NH:19][CH2:18]1)=[O:16])[CH3:13]

Participants

6

Reactant 4

HCID 312ChlorideHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 14183616Ethyl (R)-Nipecotate L-Tartrate

Product 1

HCID 98969Ethyl nipecotateYield 139.9%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

A mixture of the above crude chloride (1.14 g, 3.5 mmol), (R)-3-piperidinecarboxylic acid ethyl ester (L)-tartrate (1.05 g, 3.5 mmol), dried potassium carbonate (1.94 g, 14 mmol), sodium iodide (0.53 g, 3.5 mmol) and 2-butanone (15 ml) was heated at reflux temperature for 60 h. The reaction mixture was filtered, the filtrate washed with 2-butanone (10 ml) and the combined filtrates evapoated in vacuo. The crude product was purified by column chromatography on silica gel using a mixture of ethyl acetate and heptane (1:3) containing triethylamine (2.5%) as eluent. This afforded the product, (R)-1-(3-2-chloro-12H-dibenzo[d,g][1,3,6]dioxazocin-12-yl)-1-propyl)-3-piperidinecarboxylic acid ethyl ester (0.77 g, 49%) as an oil.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 60 h
  3. filtrationThe reaction mixture was filtered
  4. washthe filtrate washed with 2-butanone (10 ml)
  5. customThe crude product was purified by column chromatography on silica gel using
  6. additiona mixture of ethyl acetate and heptane (1:3)
  7. additioncontaining triethylamine (2.5%) as eluent

Sources & evidence

ORD record
ord-2120b3b51580490e861a99a9aec3af58
Source dataset
uspto-grants-1999_06
Patent number
US05917047

Reaction notes

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