Isopropyl Acetate → (R)-3-(4-Methoxybenzyl)-2-oxothiazolidine-4-carboxylic Acid

HRID 1445366Notes

Reaction equation

HRID 1445366 reaction equation
[SH:1][CH2:2][C@H:3]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)[C:4]([OH:6])=[O:5].[C:17]([O-])([O-])=[O:18].[K+].[K+].C1N=CN(C(N2C=NC=C2)=O)C=1.C(OC(C)C)(=O)C>C(#N)C.O>[CH3:16][O:15][C:12]1[CH:11]=[CH:10][C:9]([CH2:8][N:7]2[C@H:3]([C:4]([OH:6])=[O:5])[CH2:2][S:1][C:17]2=[O:18])=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 7915Isopropyl AcetateHCID 11430Potassium CarbonateHCID 682631,1'-CarbonyldiimidazoleHCID 13891591(R)-3-Mercapto-2-(4-methoxybenzylamino)propanoic Acid

Product 1

HCID 11207876(R)-3-(4-Methoxybenzyl)-2-oxothiazolidine-4-carboxylic AcidYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

A 22 L three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer was charged with the title compound from Example 2 (400.0 g, 1.66 mol), K2CO3 (480.0 g, 3.47 mol) and water (2.8 L). The mixture was heated at 40° C. while stirring until it became homogeneous and was then cooled to room temperature. A solution of N,N-carbonyldiimidazole (400.0 g, 222.47 mol) in acetonitrile (2.8 L) was added dropwise at a rate that maintained an internal reaction temperature less than 30° C. The reaction was monitored by HPLC and was complete upon the disappearance of the starting material (about 15 minutes). The acetonitrile was removed by heating at 40° C. and 80-100 torr. Isopropyl acetate (200 mL) was added and the pH of the mixture was adjusted to 2 with 3 M H2SO4. The biphasic mixture was filtered, and the organic phase was isolated. Additional isopropyl acetate was added and the solution was dried by azeotropic distillation. The reaction volume was reduced further until a precipitate began to form. The yellow precipitate was isolated by filtration and dried at 50° C. overnight to afford the title compound (310 g, 70%).

Workup

  1. customA 22 L three-necked round bottom flask fitted with an internal temperature probe and a mechanical stirrer
  2. temperaturewas then cooled to room temperature
  3. temperaturemaintained an internal reaction temperature less than 30° C
  4. customwas complete upon the disappearance of the starting material (about 15 minutes)
  5. customThe acetonitrile was removed
  6. temperatureby heating at 40° C.
  7. additionIsopropyl acetate (200 mL) was added
  8. filtrationThe biphasic mixture was filtered
  9. customthe organic phase was isolated
  10. customthe solution was dried by azeotropic distillation
  11. customto form
  12. customThe yellow precipitate was isolated by filtration
  13. customdried at 50° C. overnight

Sources & evidence

ORD record
ord-e8b52d4dbbeb4d0b9322f785959c93a2
Source dataset
uspto-grants-2010_02
Patent number
US07666861B2

Reaction notes

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