4-Methylmorpholine → (3-(3,4-Dimethoxyphenyl)-5-oxopyrrolidin-3-yl)acetic acid ethyl ester

HRID 399977Notes

Reaction equation

HRID 399977 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2([CH2:16]CO)[CH2:15][CH2:14][NH:13][CH2:12]2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CN1CCO[CH2:22][CH2:21]1.C[O:27]C1C=C(C=C(OC)C=1OC)C(Cl)=O.[C:41](=[O:43])=[O:42].CC(C)=O>ClCCl>[CH2:21]([O:42][C:41](=[O:43])[CH2:16][C:11]1([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:15][C:14](=[O:27])[NH:13][CH2:12]1)[CH3:22]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 153920213-(3,4-Dimethoxyphenyl)-3-(2-hydroxyethyl)pyrrolidineHCID 18522661Acetone cardice

Product 1

HCID 15392020(3-(3,4-Dimethoxyphenyl)-5-oxopyrrolidin-3-yl)acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

2-[3-(3,4-Dimethoxy-phenyl)-pyrrolidin-3-yl]-ethanol (2.27 g, 9.03 mmol) and dichloromethane (100 mL) were combined. 4-Methylmorpholine (2.28 mL, 22.6 mmol, 2.5 eq.) was added. The mixture was cooled in a ice/NaCl bath and a solution of 3,4,5-trimethoxy-benzoyl chloride (2.19 g, 9.48 mmol) in dichloromethane (30 mL) was added dropwise. After the addition was complete, the dry-ice/acetone bath was changed to an ice bath and the mixture was allowed to warm to ambient temperature and maintained overnight. The solution was extracted with 1N HCl (3×100 mL), saturated K2CO3 (3×100 mL). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to obtain a residue. The residue was purified by chromatography on silica gel eluting with ethyl acetate/methanol (20:1) to obtain a residue. The residue was dissolved in dichloromethane (50 mL), extracted with water (2×50 mL), dried over Na2SO4, filtered, and concentrated in vacuo to obtain a residue. Heated at 110° C./0.3 Torr for 16 h to obtain the title compound: Rf =0.14 (silica gel, 20:1 ethyl acetate/methanol), mp=60°-62° C. Analysis: calculated for C24H31 NO7, C 64.70; H 7.01; N 3.14; Found C 64.40; H 7.21; N 2.85.

Workup

  1. temperatureThe mixture was cooled in a ice/NaCl bath
  2. additionAfter the addition
  3. temperaturemaintained overnight
  4. extractionThe solution was extracted with 1N HCl (3×100 mL), saturated K2CO3 (3×100 mL)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto obtain a residue
  9. customThe residue was purified by chromatography on silica gel eluting with ethyl acetate/methanol (20:1)
  10. customto obtain a residue
  11. extractionextracted with water (2×50 mL)
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customto obtain a residue
  16. temperatureHeated at 110° C./0.3 Torr for 16 h

Sources & evidence

ORD record
ord-8afde2e4b0824d17b306595fb6ab9aed
Source dataset
uspto-grants-1998_10
Patent number
US05824690

Reaction notes

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