Chloroform → cis-(+-)-N-(2-(2,6-Dimethyl-1-piperidinyl)ethyl)-2-oxo-3-hydroxy-1-pyrrolidineacetamide

HRID 1906282Notes

Reaction equation

HRID 1906282 reaction equation
[OH:1][CH:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]([OH:10])=O)[C:3]1=[O:11].O[N:13]1C(=O)CC[C:14]1=O.C1(N=[C:27]=[N:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)CCCCC1.[CH:35](Cl)(Cl)Cl>CN(C)C=O>[CH3:30][C@H:31]1[CH2:32][CH2:33][CH2:34][C@@H:29]([CH3:35])[N:28]1[CH2:27][CH2:14][NH:13][C:8](=[O:10])[CH2:7][N:4]1[CH2:5][CH2:6][CH:2]([OH:1])[C:3]1=[O:11]

Participants

6

Reactant 4

HCID 6212Chloroform2×HCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 19817647(R/S)-2-(3-hydroxy-2-oxo-1-pyrrolidinyl)acetic acid

Product 1

HCID 3069833cis-(+-)-N-(2-(2,6-Dimethyl-1-piperidinyl)ethyl)-2-oxo-3-hydroxy-1-pyrrolidineacetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.50 g of (R/S)-2-(3-hydroxy-2-oxo-1-pyrrolidinyl)acetic acid are dissolved in 50 ml of chloroform and 10 ml of dimethylformamide. 1.08 g of N-hydroxysuccinimide are added thereto. Thereafter, 2.08 g of dicyclohexylcarbodiimide dissolved in 25 ml of chloroform are added. The mixture is stirred at room temperature for 4 hours and then the precipitated solid is filtered. The filtrate is concentrated to a volume of about 20 ml and then again filtered. The filtrate is evaporated and the residue is treated with 1.70 g of 94.7% cis-2-(2,6-dimethyl-1-piperidinyl)ethylamine. The mixture is left to stand at room temperature overnight and the excess cis-2-(2,6-dimethyl-1-piperidinyl)ethylamine is removed in vacuo. The residue is chromatographed on 60 g of aluminum oxide (activity grade I, basic). The fractions which are eluted with chloroform and alcohol are evaporated. The residue is stirred at room temperature in 35 ml of diethyl ether/ethyl acetate (2:1). There is obtained (R/S)-cis-N-[2-(2,6-dimethyl-1-piperidinyl)ethyl] -2-(3-hydroxy-2-oxo-1-pyrrolidinyl)acetamide (melting point 116°-120°) which melts at 126°-128° after repeated chromatography on aluminum oxide (activity grade III, neutral) and recrystallization from ethyl acetate.

Workup

  1. additionare added
  2. filtrationthe precipitated solid is filtered
  3. concentrationThe filtrate is concentrated to a volume of about 20 ml
  4. filtrationagain filtered
  5. customThe filtrate is evaporated
  6. additionthe residue is treated with 1.70 g of 94.7% cis-2-(2,6-dimethyl-1-piperidinyl)ethylamine
  7. waitThe mixture is left
  8. waitto stand at room temperature overnight
  9. customthe excess cis-2-(2,6-dimethyl-1-piperidinyl)ethylamine is removed in vacuo
  10. customThe residue is chromatographed on 60 g of aluminum oxide (activity grade I, basic)
  11. washThe fractions which are eluted with chloroform and alcohol
  12. customare evaporated
  13. stirringThe residue is stirred at room temperature in 35 ml of diethyl ether/ethyl acetate (2:1)

Sources & evidence

ORD record
ord-1d14ed0d79d242178873c211e0a24a35
Source dataset
uspto-grants-1987_03
Patent number
US04650878

Reaction notes

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