Water → 1-(Phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate

HRID 1172162Notes

Reaction equation

HRID 1172162 reaction equation
Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[OH:12][C@H:13]1[CH2:17][NH:16][C@H:15]([C:18]([OH:20])=[O:19])[CH2:14]1.C([O-])(O)=O.[Na+].O>CCOCC>[CH2:5]([O:4][C:2]([N:16]1[CH2:17][C@H:13]([OH:12])[CH2:14][C@H:15]1[C:18]([OH:20])=[O:19])=[O:3])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5810L-HydroxyprolineHCID 10387Benzyl chloroformateHCID 516892Sodium Bicarbonate

Product 1

HCID 3915171-(Phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylateYield 78%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of benzyl chloroformate (50 mL, 0.35 mol) in Et2O (160 mL) was added dropwise, during 10 min, to a rapidly stirred mixture of trans-4-hydroxy-L-proline (39.8 g, 0.308 mol), NaHCO3 (63.7 g, 0.758 mol) and H2O (660 mL). The reaction mixture was stirred at room temperature for 20 h. The layers were separated, and the aqueous layer was washed with Et2O (4×200 mL), cooled, and then acidified to pH 1-2 with concentrated hydrochloric acid. The resulting emulsion was extracted with EtOAc (5×200 mL). Combined EtOAc extracts were washed in succession with H2O (3×500 mL) and brine (3×500 mL), dried over MgSO4, and then concentrated in vacuo to give intermediate (4) as a colorless foam (62.7 g, 78%). Additional reactions were carried out to give a total of 284 g of product suitable for further transformation.

Workup

  1. customThe layers were separated
  2. washthe aqueous layer was washed with Et2O (4×200 mL)
  3. temperaturecooled
  4. extractionThe resulting emulsion was extracted with EtOAc (5×200 mL)
  5. washCombined EtOAc extracts were washed in succession with H2O (3×500 mL) and brine (3×500 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fdf83dd35ae14b1dbcc3c06adc8b1e9f
Source dataset
uspto-grants-2010_11
Patent number
US07834005B2

Reaction notes

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