Cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid → 8-Benzyl-3-methyl-3,8-diazabicyclo[3.2.1]octane-2,4-dione

HRID 1605944Notes

Reaction equation

HRID 1605944 reaction equation
[CH3:1][NH:2][C:3]([C@H:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@@H:8]([C:17]([OH:19])=O)[CH2:7][CH2:6]1)=[O:4]>C(OC(=O)C)(=O)C>[CH2:10]([N:9]1[CH:5]2[CH2:6][CH2:7][CH:8]1[C:17](=[O:19])[N:2]([CH3:1])[C:3]2=[O:4])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

3

Reactant 1

HCID 68128237Cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid

Product 1

HCID 215454938-Benzyl-3-methyl-3,8-diazabicyclo[3.2.1]octane-2,4-dione

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Procedure

Cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid (32.3 g, 0.123 mole) and acetic anhydride (160 ml) were heated together at 100° C for 45 minutes after all of the solid had dissolved. Removal of solvent in vacuo left a red-brown oil that was dissolved in a minimum amount of benzene. After removal of 2.0 g of unreacted cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid by filtration, the solution of desired product was chromatographed on 900 g alumina with benzene elution to give 13.2 g (44%) of pure, oily 8-benzyl-3-methyl-3,8-diazabicyclo[3.2.1]octane-2,4-dione. Treatment of a sample with excess ethanolic hydrogen chloride in diethyl ether solution produced a hydrochloride salt, melting point 140°-170° C. A sample of the free base, melting point 73°-75° C, was subsequently obtained by slow crystallization from benzene.

Workup

  1. dissolutionhad dissolved
  2. customRemoval of solvent in vacuo
  3. waitleft a red-brown oil that
  4. dissolutionwas dissolved in a minimum amount of benzene
  5. customAfter removal of 2.0 g of unreacted cis-5-(N-methylcarbamyl)-1-benzylpyrrolidine-2-carboxylic acid
  6. filtrationby filtration
  7. customthe solution of desired product was chromatographed on 900 g alumina with benzene elution

Sources & evidence

ORD record
ord-b38e111d29774f7283d9505cff9b3cbf
Source dataset
uspto-grants-1976_04
Patent number
US03951980

Reaction notes

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