Water → HCID 12968959, compound

HRID 1956892Notes

Reaction equation

HRID 1956892 reaction equation
O.[NH2:2][C@H:3]([C:9]([OH:11])=[O:10])[CH2:4][CH2:5][C:6](=[O:8])[NH2:7].[OH-].[Na+].[Cl:14][CH2:15][C:16](Cl)=[O:17]>C1(C)C=CC=CC=1>[Cl:14][CH2:15][C:16]([NH:2][C@H:3]([C:9]([OH:11])=[O:10])[CH2:4][CH2:5][C:6](=[O:8])[NH2:7])=[O:17]

Participants

6

Reactant 4

HCID 962WaterHCID 5961L-GlutamineHCID 6577Chloroacetyl chlorideHCID 14798Sodium Hydroxide2×

Product 1

HCID 12968959HCID 12968959, compoundYield 89.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a mixed solvent of 1750 ml of water and 497 ml of toluene was added 733.7 g (5 mol) of L-glutamine at room temperature. The solution was cooled to 0° to 5° C. and adjusted to pH 11 with 5N sodium hydroxide. To the solution was added dropwise a solution of 565.3 g (5 mol) of chloro-acetyl chloride in 497 ml of toluene while maintaining the pH of the reaction mixture at 11 with 5N sodium hydroxide. After stirring at 0° to 5° C. for 1 hour, toluene was removed from the reaction mixture by liquid-liquid separation. The aqueous layer separated was adjusted to pH 2 by addition of 410 ml of concentrated hydrochloric acid. After seeding, the reaction mixture was subjected to crystallization at room temperature for 1 hour and then at 0° to 5° C. for 3 hours. The resulting crystals were collected by filtration and dried under reduced pressure to give 992.6 g (89.2 mole percent (mol %) yield) of crude N-chloroacetyl-L-glutamine (sodium chloride content: 13.6 weight percent (wt %)). The crystals were analyzed by high performance liquid chromatography (HPLC) (column: Shim-pack CLC-ODS, 6 ×150 mm (manufactured by Shimadzu Corporation); eluent: 0.01M sodium 1-octanesulfonate/0.01M KH2PO4 buffer (pH 2.5)/1% methanol; detection: UV 210 nm). The purity of the crystals was found to be 99.0% as calculated from the HPLC relative area ratio.

Workup

  1. temperatureThe solution was cooled to 0° to 5° C.
  2. customtoluene was removed from the reaction mixture by liquid-liquid separation
  3. customThe aqueous layer separated
  4. additionwas adjusted to pH 2 by addition of 410 ml of concentrated hydrochloric acid
  5. customthe reaction mixture was subjected to crystallization at room temperature for 1 hour
  6. waitat 0° to 5° C. for 3 hours
  7. filtrationThe resulting crystals were collected by filtration
  8. customdried under reduced pressure

Sources & evidence

ORD record
ord-2543992175844483ac52d2e2e9a4e60e
Source dataset
uspto-grants-1998_07
Patent number
US05780677

Reaction notes

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