Pyrrole → (-)-Epibatidine-L-tartrate

HRID 399085Notes

Reaction equation

HRID 399085 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[Cl:6][C:7](OC1C(C(C)C)CCC(C)C1)=O.ClC#CS(C1C=C(C2C=CC=CN=2)C=CC=1)(=O)=O.[CH:38]12[NH:44][CH:41]([CH:42]=[CH:43]1)[CH:40]=[CH:39]2.Br.CC(O)=O>[Na].[Hg]>[CH:3]1[C:4]([CH:43]2[CH:38]3[NH:44][CH:41]([CH2:40][CH2:39]3)[CH2:42]2)=[CH:5][N:1]=[C:7]([Cl:6])[CH:2]=1

Participants

7

Reactant 5

HCID 8027Pyrrole2×HCID 1389217-AzanorbornadieneHCID 151928Menthyl chloroformateHCID 21893785Acetic Acid Mixture with Hydrobromic AcidHCID 702361512-Chloro-5-pyridyl phenylsulfonyl acetylene

Product 1

HCID 1204(-)-Epibatidine-L-tartrate

Reagents, catalysts & solvents 1

HCID 9837419Sodium amalgamCatalyst

Procedure

N-carbo-(-)-menthyloxy pyrrole is prepared from pyrrole and (-)-menthyl chloroformate by the method described above. The chiral pyrrole is treated with the sulfonyl acetylene 22 or 34 as in Example 29 to give a diastereoisomeric mixture of the chiral cycloadduct 7-aza-bicyclo[2.2.1]hepta-2,5-diene derivative. After treatment with sodium amalgam as in Example 30, the diastereoisomeric mixture of 2-exo-aryl-7-aza-bicyclo[2.2.1]hepta-5-ene derivatives is obtained. These diastereomers are separated by chromatography to give the d and 1 enantiomers. The optically active intermediates are each reduced and treated with HBr/AcOH to yield optically active epibatidine enantiomers. Similarly, other substituted 7-aza-bicyclo[2,2,1]heptane analogs are prepared from the corresponding chiral pyrroles and chiral cycloadducts.

Workup

  1. customto give
  2. customis obtained
  3. customThese diastereomers are separated by chromatography
  4. customto give the d and 1 enantiomers

Sources & evidence

ORD record
ord-10ffec6b695f4e01b9ea8420202122b2
Source dataset
uspto-grants-1998_10
Patent number
US05817679

Reaction notes

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