Benzoyl chloride → n-Benzoyl-cis-4-hydroxy-d-proline methyl ester

HRID 432954Notes

Reaction equation

HRID 432954 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:11])[C@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][NH:6]1.C(=O)(O)[O-].[Na+].[C:17](Cl)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>ClCCl>[CH3:2][O:3][C:4](=[O:11])[C@H:5]1[CH2:9][C@@H:8]([OH:10])[CH2:7][N:6]1[C:17](=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 516892Sodium BicarbonateHCID 12764090Methyl (2R,4R)-4-hydroxypyrrolidine-2-carboxylate hydrochloride

Product 1

HCID 1476248n-Benzoyl-cis-4-hydroxy-d-proline methyl esterYield 90.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

This ester was added in portions to a stirred mixture of 1500 mL of 1 N aqueous sodium bicarbonate and 500 mL of dichloromethane at 0-5° C., then 80 mL (97 g, 0.69 mol) of benzoyl chloride was added dropwise at 0-5° C., and the mixture was stirred at room temperature overnight. The phases were separated and the aqueous phase was extracted with dichloromethane (twice with 250 mL). The organic phases were combined, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was triturated with toluene to afford 112.98 g (90.7% from cis4-hydroxy-D-proline) of N-benzoyl-cis-4-hydroxy-D-proline methyl ester as a white powder.

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with dichloromethane (twice with 250 mL)
  3. dry with materialdried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was triturated with toluene

Sources & evidence

ORD record
ord-2292fd3a4d614286975d733427428fea
Source dataset
uspto-grants-2003_12
Patent number
US06664400B2

Reaction notes

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