Thionyl Chloride → 3-Fluorobenzyl quinuclidine-4-carboxylate

HRID 1910521Notes

Reaction equation

HRID 1910521 reaction equation
Cl.[N:2]12[CH2:9][CH2:8][C:5]([C:10]([OH:12])=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.S(Cl)(Cl)=O.[F:17][C:18]1[CH:19]=[C:20]([CH2:24]O)[CH:21]=[CH:22][CH:23]=1>>[N:2]12[CH2:9][CH2:8][C:5]([C:10]([O:12][CH2:24][C:20]3[CH:21]=[CH:22][CH:23]=[C:18]([F:17])[CH:19]=3)=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2

Participants

4

Reactant 3

HCID 24386Thionyl ChlorideHCID 680083-Fluorobenzylic alcoholHCID 667378251-Azabicyclo(2.2.2)octane-4-carboxylic acid hydrochloride

Product 1

HCID 709257943-Fluorobenzyl quinuclidine-4-carboxylateYield 29.9%

Procedure

A mixture of quinuclidine-4-carboxylic acid hydrochloride (100 mg, 0.52 mmol) and thionyl chloride (500 μl, 6.85 mmol) was refluxed for 2 hours. The reaction was cooled to room temperature, and the solvent was accurately removed. The residue was suspended in dry DCM and treated with (3-fluorophenyl)methanol (65.8 mg, 0.52 mmol). The reaction was stirred at room temperature for 24 hours. The solvent was evaporated, and the residue was dissolved in water (1 ml), basified with NaHCO3 and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and evaporated to obtain 3-fluorobenzyl quinuclidine-4-carboxylate (41 mg, 29.8% yield), which was used in the next step without any further purification.

Workup

  1. temperaturewas refluxed for 2 hours
  2. customthe solvent was accurately removed
  3. customThe solvent was evaporated
  4. dissolutionthe residue was dissolved in water (1 ml)
  5. extractionextracted twice with EtOAc
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-f0e4b0f5ec744a9991040d1bf7eda0f5
Source dataset
uspto-grants-2013_12
Patent number
US08604015B2

Reaction notes

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