Formaldehyde → Dimethyl (3R,4S)-1-benzylpyrrolidine-3,4-dicarboxylate

HRID 478776Notes

Reaction equation

HRID 478776 reaction equation
[CH2:1]([NH:8][CH2:9]C(O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:13]([O:21][CH3:22])(=[O:20])/[CH:14]=[CH:15]\[C:16]([O:18][CH3:19])=[O:17].C=O.[CH3:25]CN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:9][C@H:15]([C:16]([O:18][CH3:19])=[O:17])[C@H:14]([C:13]([O:21][CH3:22])=[O:20])[CH2:25]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 869652-(Benzylamino)acetic acidHCID 5271565Dimethyl maleate

Product 1

HCID 10978757Dimethyl (3R,4S)-1-benzylpyrrolidine-3,4-dicarboxylateYield 34.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of N-benzylglycine (12.39 g, 75 mmol), dimethyl maleate (6.26 g, 50 mmol), paraformaldehyde (4.5 g, 150 mmol) and DIEA (8.7 mL, 50 mmol) in toluene (100 mL) was stirred at reflux for 2 hours and concentrated. The residue was taken up in EtOAc. The solution was washed with brine 3×, dried (MgSO4) and concentrated. Column chromatography eluting with 50% EtOAc/hexanes provided dimethyl cis-1-benzyl-3,4-pyrrolidinedicarboxylate (4.8 g, 34%). MS (M+H)+=278.5.

Workup

  1. temperatureat reflux for 2 hours
  2. concentrationconcentrated
  3. washThe solution was washed with brine 3×
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. washColumn chromatography eluting with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-46dd9d23806947f28dc42014a3fe4a85
Source dataset
uspto-grants-2003_11
Patent number
US06642255B2

Reaction notes

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