L-(+)-Cysteine → (4R)-2-(4-Methoxyphenyl)-4-thiazolidinecarboxylic acid

HRID 1664241Notes

Reaction equation

HRID 1664241 reaction equation
O.Cl.[NH2:3][C@H:4]([C:7]([OH:9])=[O:8])[CH2:5][SH:6].C([O-])(=O)C.[Na+].N[C@H](C(O)=O)CS.[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][CH:25]=1>C(O)C.O>[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]=[O:29])=[CH:26][CH:25]=1.[CH3:22][O:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]2[NH:3][C@H:4]([C:7]([OH:9])=[O:8])[CH2:5][S:6]2)=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 5862L-(+)-CysteineHCID 23462L-Cysteine hydrochloride monohydrateHCID 312444-MethoxybenzaldehydeHCID 517045Sodium Acetate

Product 2

HCID 312444-MethoxybenzaldehydeHCID 6610613(4R)-2-(4-Methoxyphenyl)-4-thiazolidinecarboxylic acidYield 90%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

A 22 L three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer was charged with L-cysteine hydrochloride monohydrate (500.0 g, 2.85 mol), sodium acetate (260.0 g, 3.17 mol) and water (4 L). The mixture was stirred until all of the L-cysteine dissolved. A solution of 4-methoxybenzaldehyde (426.0 g, 3.13 mol) in ethanol (3.5 L) was prepared and added to the reaction dropwise such that the internal reaction temperature was kept below 30° C. The reaction went from a clear solution to a thick white slurry during the addition of the 4-methoxybenzaldehyde solution. After 30 minutes, ethanol (3.5 L) was added to the reaction and the slurry thickened. Stirring was continued for 1 hour and then the solid was isolated by filtration, and the solid was washed with additional ethanol. The solid was dried in a vacuum oven at 50° C. over 48 hours to afford the title compound (610 g, 90%).

Workup

  1. customA 22 L three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer
  2. dissolutiondissolved
  3. additionadded to the reaction dropwise such that the internal reaction temperature
  4. customwas kept below 30° C
  5. waitwas continued for 1 hour
  6. customthe solid was isolated by filtration
  7. washthe solid was washed with additional ethanol
  8. customThe solid was dried in a vacuum oven at 50° C. over 48 hours

Sources & evidence

ORD record
ord-47d4969703fe45cc92fd7f50352a0318
Source dataset
uspto-grants-2011_10
Patent number
US08039465B2

Reaction notes

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