Citric Acid → (R)-3-(4-Methoxybenzyl)-4-acetylthiazolidin-2-one

HRID 2251757Notes

Reaction equation

HRID 2251757 reaction equation
C[Mg]Cl.CON(C)[C:7]([C@@H:9]1[CH2:13][S:12][C:11](=[O:14])[N:10]1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)=[O:8].[C:25](O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O>[C:7]([C@@H:9]1[CH2:13][S:12][C:11](=[O:14])[N:10]1[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)(=[O:8])[CH3:25]

Participants

6

Reactant 3

HCID 311Citric AcidHCID 16742592(R)-N-Methoxy-3-(4-methoxybenzyl)-N-methyl-2-oxothiazolidine-4-carboxamideHCID 178418332HCID 178418332, compound2×

Product 1

HCID 11346122(R)-3-(4-Methoxybenzyl)-4-acetylthiazolidin-2-oneYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A dry three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer was charged with a solution of methylmagnesium chloride in THF (0.805 L, 3 M). The solution was purged with nitrogen and cooled to 0° C. In a separate flask, the title compound from Example 4 (250.0 g, 0.805 mol) was dissolved in dry THF (1.0 L). This solution was added to the solution of methylmagnesium chloride at a rate that maintained an internal reaction temperature less than 5° C. The reaction was monitored by HPLC and was complete upon the disappearance of the starting material (approx. 20 minutes after completing the addition). The reaction mixture was slowly added into a 10% citric acid solution (1 L) at a rate that maintained a temperature of less than 25° C. The mixture was diluted with water, and the THF was removed by distillation at 70° C. (80° C. external) and 1 atm. The product was extracted with ethyl acetate, and the organic phase was separated and concentrated by distillation at 76° C. (95° C. external) and 1 atm to a final volume of ˜800 mL. The solution was allowed to cool to room temperature, and n-heptane was added to give a precipitate. The suspension was stirred for 30 minutes, and the solid was isolated by filtration and dried in a vacuum oven at 40° C. overnight to afford the title compound (170 g, 80%).

Workup

  1. customA dry three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer
  2. customThe solution was purged with nitrogen
  3. temperaturemaintained an internal reaction temperature less than 5° C
  4. customapprox. 20 minutes
  5. additionthe addition)
  6. temperaturethat maintained a temperature of less than 25° C
  7. customthe THF was removed by distillation at 70° C. (80° C. external) and 1 atm
  8. extractionThe product was extracted with ethyl acetate
  9. customthe organic phase was separated
  10. concentrationconcentrated by distillation at 76° C. (95° C. external) and 1 atm to a final volume of ˜800 mL
  11. temperatureto cool to room temperature
  12. additionn-heptane was added
  13. customto give a precipitate
  14. customthe solid was isolated by filtration
  15. customdried in a vacuum oven at 40° C. overnight

Sources & evidence

ORD record
ord-db2485c25ee94a248c7a07fe7943508d
Source dataset
uspto-grants-2008_01
Patent number
US07320974B2

Reaction notes

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