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

HRID 1987169Notes

Reaction equation

HRID 1987169 reaction equation
[CH2:1]([O:3][C:4](=[O:12])/[CH:5]=[CH:6]/[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH3:2].[CH2:13]([NH:20][CH2:21]C(O)=O)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH2:25]=O>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C@H:5]1[C@H:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:21][N:20]([CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:25]1)=[O:12])[CH3:2]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 869652-(Benzylamino)acetic acidHCID 638144Diethyl fumarate

Product 1

HCID 6558921diethyl (3S,4S)-1-benzylpyrrolidine-3,4-dicarboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

Fumaric acid diethylester (21.6 g; 0.126 mol) is dissolved in toluene (900 ml) and heated at 105° C. A mixture of N-benzylglycine (25 g; 0.151 mol) and paraformaldehyde (25.36 g; 0.844 mol) is added in 4 g portions to the refluxing solution. After completion of the addition the mixture is heated for 18 h at 105° C. The mixture is then evaporated to dryness and suspended in n-hexane. The insoluble material is filtered off and the remaining solution is evaporated to dryness. The crude product is used for the next step without further purification. Yield: 32.5 g (70.3%), ESI-MS: m/z=306 [M+H]+

Workup

  1. additionis added in 4 g portions to the refluxing solution
  2. additionAfter completion of the addition the mixture
  3. temperatureis heated for 18 h at 105° C
  4. customThe mixture is then evaporated to dryness
  5. filtrationThe insoluble material is filtered off
  6. customthe remaining solution is evaporated to dryness
  7. customThe crude product is used for the next step without further purification

Sources & evidence

ORD record
ord-8e905b5c320c415dba4ea4299bda3f01
Source dataset
uspto-grants-2009_06
Patent number
US07550487B2

Reaction notes

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