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

HRID 1586100Notes

Reaction equation

HRID 1586100 reaction equation
[OH:1][C@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.C([O-])(O)=O.[Na+].Cl[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].C(=O)=O>O.C1(C)C=CC=CC=1>[C:16]([N:5]1[CH2:6][C@H:2]([OH:1])[CH2:3][C@H:4]1[C:7]([OH:9])=[O:8])([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 5810L-Hydroxyproline2×HCID 10387Benzyl chloroformateHCID 516892Sodium Bicarbonate

Product 1

HCID 3915171-(Phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylateYield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

N-Benzyloxycarbonyl)-trans-4-hydroxy-L-proline. Trans-4-hydroxy-L-proline 1 (10.0 g, 76.3 mmol) and NaHCO3 (16.0 g, 190 mmol) were dissolved in H2O (165 mL), then a solution of benzyl chloroformate (12.5 mL, 15.0 g, 87.7 mmol) in toluene (40 mL) was added over a period of 15 minutes. After stirring at room temperature for 16 h, CO2 evolution had ceased and the two phases were separated. Excess benzyl chloroformate was removed from the aqueous phase by washing with ether (4×50 mL). Cooling of the aqueous phase in an ice bath, followed by acidification to pH 2 with concentrated HCl, caused the oily product to precipitate. This oil was extracted into ethyl acetate by repeated washings (5×50 mL) of the aqueous layer. Further acidification of the aqueous layer produced no more precipitate, indicating thorough removal of the product. The combined organic extracts were dried (MgSO4) and concentrated to a viscous oil, which crystallized upon standing at room temperature to provide 19.9 g (98%) of N-CBZ-trans-4-hydroxy-L-proline: mp 106°-107° C. (lit.19 mp 106°-107° C.); [α]24D-77.5° (c 1.03, CHCl3) [lit.19 [α]20D-72° (c 1.0 CHCl3)].

Workup

  1. customthe two phases were separated
  2. customExcess benzyl chloroformate was removed from the aqueous phase
  3. washby washing with ether (4×50 mL)
  4. temperatureCooling of the aqueous phase in an ice bath
  5. customto precipitate
  6. extractionThis oil was extracted into ethyl acetate by repeated washings (5×50 mL) of the aqueous layer
  7. customFurther acidification of the aqueous layer produced no more precipitate
  8. customremoval of the product
  9. dry with materialThe combined organic extracts were dried (MgSO4)
  10. concentrationconcentrated to a viscous oil, which
  11. customcrystallized
  12. customupon standing at room temperature

Sources & evidence

ORD record
ord-9940b4840a11412282450ef174590f4a
Source dataset
uspto-grants-1999_08
Patent number
US05942537

Reaction notes

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