Dimethyl itaconate → Methyl 1-(4-methoxybenzyl)-5-oxopyrrolidine-3-carboxylate

HRID 1295794Notes

Reaction equation

HRID 1295794 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH2:8])=[CH:5][CH:4]=1.[C:11]([O:20][CH3:21])(=[O:19])[C:12]([CH2:14][C:15](OC)=[O:16])=[CH2:13].OC1C=CC=CN=1>CO.C1(C)C=CC=CC=1>[CH3:21][O:20][C:11]([CH:12]1[CH2:14][C:15](=[O:16])[N:8]([CH2:7][C:6]2[CH:9]=[CH:10][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH2:13]1)=[O:19]

Participants

6

Reactant 3

HCID 69240Dimethyl itaconateHCID 754524-MethoxybenzylamineHCID 178516071HCID 178516071, compound

Product 1

HCID 4093874Methyl 1-(4-methoxybenzyl)-5-oxopyrrolidine-3-carboxylateYield 85.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

In a 250 ml three necked flask fitted with a magnetic stirrer and reflux condenser, under inert atmosphere, 10 g (73 mmol, 1 eq) of 4-methoxy-benzylamine and 12.7 g (81 mmol, 1.1 eq) of dimethyl itaconate are dissolved in 100 ml of MeOH. The mixture is brought to reflux for 10 h, and cooled down slowly to 20° C. over 4 h and concentrated to dryness. In a 250 ml three necked flask fitted with a magnetic stirrer and Rashig column and distillation arm, under inert atmosphere, the crude intermediate and 0.69 g (7.30 mmol, 0.1 eq) of 2-hydroxypyridine are dissolved in 200 ml of toluene. The mixture is brought to reflux and the methanol formed distilled off for 8 h, until no more methanol is collected. Temperature in the pot reached 112° C. The mixture is cooled down and concentrated to dryness to give the crude ester. It is purified by column chromatography on silicagel (AcOEt/n-Hexane: 1/1 (v/v)) to afford the pure ester a1 (16.48 g, 85.9%).

Workup

  1. temperaturereflux condenser
  2. temperatureto reflux for 10 h
  3. concentrationconcentrated to dryness
  4. customIn a 250 ml three necked flask fitted with a magnetic stirrer
  5. distillationRashig column and distillation arm
  6. temperatureto reflux
  7. distillationdistilled off for 8 h, until no more methanol
  8. customis collected
  9. custompot reached 112° C
  10. temperatureThe mixture is cooled down
  11. concentrationconcentrated to dryness
  12. customto give the crude ester
  13. customIt is purified by column chromatography on silicagel (AcOEt/n-Hexane: 1/1 (v/v))

Sources & evidence

ORD record
ord-4ffb4fad867844928bd5925445c46d94
Source dataset
uspto-grants-2007_07
Patent number
US07244747B2

Reaction notes

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