Toluene → 1-Phenyl-cycloheptanecarboxylic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

HRID 2192297Notes

Reaction equation

HRID 2192297 reaction equation
[CH3:1][O:2][C:3]([C:5]1([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].[N:18]12[CH2:25]C[CH:21]([CH2:22][CH2:23]1)[C@@H:20](O)[CH2:19]2.[Na].C1(C)C=CC=CC=1>CCCCCCC>[N:18]12[CH2:23][CH2:22][CH:21]([CH2:20][CH2:19]1)[C@@H:1]([O:2][C:3]([C:5]1([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4])[CH2:25]2

Participants

6

Reactant 4

HCID 1140TolueneHCID 914043-Quinuclidinol, (-)-HCID 5360545SodiumHCID 59179615Methyl 1-phenylcycloheptanecarboxylate

Product 1

HCID 591796191-Phenyl-cycloheptanecarboxylic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)esterYield 82.7%

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent2×

Procedure

1-Phenyl-cycloheptanecarboxylic acid methyl ester (Example 1d) (1.0 g) and (R)-quinuclidin-3-ol (0.39 g) were refluxed in heptane (50 mL) containing sodium (˜5 mg in a Dean and Stark apparatus for 24 hours. Heptane (20 mL) was replaced with toluene (20 mL) and the reflux was continued for 3 days. The reaction was partitioned between water (50 mL) and ether (50 mL) and the ether layer was separated, dried (MgSO4) and evaporated. The crude product was purified by column chromatography on silica elutting with ethyl acetate/triethylamine (99/1) to afford the titled compound as an oil (0.83 g).

Workup

  1. customThe reaction was partitioned between water (50 mL) and ether (50 mL)
  2. customthe ether layer was separated
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe crude product was purified by column chromatography on silica elutting with ethyl acetate/triethylamine (99/1)

Sources & evidence

ORD record
ord-13fa6d6ab0b44db8b121b6816857ef98
Source dataset
uspto-grants-2012_12
Patent number
US08329729B2

Reaction notes

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