Benzaldehyde → (S)-1-Benzyl-5-carboxy-2-pyrrolidinone

HRID 2050934Notes

Reaction equation

HRID 2050934 reaction equation
[NH2:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5]([OH:7])=O.[Na].[OH-].[Na+].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[BH4-].[Na+]>O.C(=O)C1C=CC=CC=1>[O:7]=[C:5]1[N:1]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4]1

Participants

8

Reactant 5

HCID 240BenzaldehydeHCID 14798Sodium HydroxideHCID 33032L-Glutamic AcidHCID 4311764Sodium borohydride2×HCID 5360545Sodium

Product 1

HCID 10900113(S)-1-Benzyl-5-carboxy-2-pyrrolidinoneYield 55%

Reagents, catalysts & solvents 2

HCID 240BenzaldehydeCatalystHCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

L-Glutamic acid, monosodium salt (250 g, 1.33 mol) was added at room temperature to a solution of sodium hydroxide (53.6 g, 1.34 mol) in 550 mL of water. To the resulting solution was added benzaldehyde (142.3 g, 1.34 mol). The mixture was stirred and cooled to 10° C. and sodium borohydride (15.2 g, 0.409 mol) was added in portions, keeping the temperature at 10°-15° C. The mixture was stirred for 30 min, and another portion of benzaldehyde (7.5 g, 0.07 mol) was added. After 10 min, a second portion of sodium borohydride (3.7 g, 0.10 mol) was added as before. The mixture was then allowed to stir at room temperature overnight. The solution was washed with methylene chloride (250 mL, discarded), and acidified to pH 3 with 6N HCl. The paste, consisting of N-(phenylmethyl)-L-glutamic acid, was diluted with 500 mL of H2O and heated to reflux overnight. The resulting solution was cooled to room temperature and extracted with chloroform. The combined extracts were washed with brine, dried over Na2SO4, and concentrated on a rotary evaporator to give 160 g (55% yield) of (S)-5-oxo-1-(phenylmethyl)-2-pyrrolidinecarboxylic acid as a white solid.

Workup

  1. customat 10°-15° C
  2. stirringThe mixture was stirred for 30 min
  3. stirringto stir at room temperature overnight
  4. washThe solution was washed with methylene chloride (250 mL, discarded)
  5. additionwas diluted with 500 mL of H2O
  6. temperatureheated
  7. temperatureto reflux overnight
  8. temperatureThe resulting solution was cooled to room temperature
  9. extractionextracted with chloroform
  10. washThe combined extracts were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-70056d5460b54fe2a2006fbc9c2ef916
Source dataset
uspto-grants-1991_05
Patent number
US05015653

Reaction notes

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