Water → (3S)-5-Oxo-4-(phenylmethyl)-3-morpholinecarboxylic acid

HRID 895659Notes

Reaction equation

HRID 895659 reaction equation
[CH2:1]([NH:8][C@H:9]([C:12]([OH:14])=[O:13])[CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].O.Cl[CH2:19][C:20](Cl)=[O:21]>C(#N)C>[CH2:1]([N:8]1[C:20](=[O:21])[CH2:19][O:11][CH2:10][C@H:9]1[C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6577Chloroacetyl chlorideHCID 14798Sodium HydroxideHCID 853606(2S)-2-(benzylamino)-3-hydroxypropanoic acid

Product 1

HCID 13543372(3S)-5-Oxo-4-(phenylmethyl)-3-morpholinecarboxylic acidYield 25%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A 5 L 3-neck round bottom flask was charged with (S)-(+)-N-benzylserine (229 g, 1.17 mol), sodium hydroxide (58.7 g, 1.47 mol), and water (1 L). The resulting solution was cooled to 0° C. and chloroacetyl chloride (170.4 g, 1.5 mol) added dropwise at a rate to maintain the temperature below 4° C. After addition was complete the reaction was stirred at 0° C. for 30 minutes. The cold bath was then removed and a solution of 30% sodium hydroxide (350 mL) added. An exotherm was observed and the reaction temperature reached 29° C. The reaction mixture was further heated to 33° C. and maintained at this temperature for 2 hours. Cooling to room temperature followed by acidification to pH 1 with 37% hydrochloric acid resulted in the formation of a thick white precipitate, which was isolated by filtration. The filter cake was slurried in acetonitrile (1 L), filtered, and the filtrate concentrated. Drying of the resulting solid afforded 68.1 g (25%) of (S)-(+)-4-benzylmorpholin-5-one-3-carboxylic acid as a crystalline white solid.

Workup

  1. temperatureto maintain the temperature below 4° C
  2. additionAfter addition
  3. customThe cold bath was then removed
  4. additiona solution of 30% sodium hydroxide (350 mL) added
  5. customreached 29° C
  6. temperatureThe reaction mixture was further heated to 33° C.
  7. temperaturemaintained at this temperature for 2 hours
  8. temperatureCooling to room temperature
  9. customresulted in the formation of a thick white precipitate
  10. customwhich was isolated by filtration
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated
  13. customDrying of the resulting solid

Sources & evidence

ORD record
ord-8be1cd158a274feb905834d35faacd0d
Source dataset
uspto-grants-2005_07
Patent number
US06916815B2

Reaction notes

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