1-Chloroethyl chloroformate → HCID 22495527, compound

HRID 1815838Notes

Reaction equation

HRID 1815838 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[C:22]3[O:21][CH:20]=[CH:19][C:18]=3[CH:17]=[C:16]([F:23])[CH:15]=2)=[C:10]([CH3:24])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClCCCl>[CH3:24][C:10]1[CH2:9][NH:8][CH2:13][CH2:12][C:11]=1[C:14]1[C:22]2[O:21][CH:20]=[CH:19][C:18]=2[CH:17]=[C:16]([F:23])[CH:15]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 22495538HCID 22495538, compound

Product 1

HCID 22495527HCID 22495527, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 0.45 gm (1.42 mMol) 1-benzyl-3-methyl-4-(5-fluorobenzofur-7-yl)-1,2,5,6-tetrahydropyridine in 15 mL 1,2-dichloroethane was cooled to 0° C. To this solution was then added 0.40 mL (3.7 mMol) 1-chloroethyl chloroformate dropwise. The reaction was heated to reflux for 4 hours and was then concentrated under reduced pressure. The residue was dissolved in methanol and then placed on an SCX column, eluting with methanol followed by 0.5 N ammonia in methanol. Fractions containing the desired free base were combined and concentrated under reduced pressure. This residue was subjected to silica gel chromatography, eluting with a gradient of dichloromethane containing 0-6% methanol, and then with 9:1:0.1 dichloromethane:methanol:ammonium hydroxide. Fractions containing product were combined and concentrated under reduced pressure to provide 0.26 gm (81%) of 3-methyl-4-(5-fluorobenzofur-7-yl)-1,2,5,6-tetrahydropyridine. A solution of 0.21 gm (0.92 mMol) of this free amine in ethanol was heated at reflux and then 0.11 gm (0.92 mMol) fumaric acid were added. The mixture was stirred at reflux for about 5 minutes and was then concentrated under reduced pressure. The residue was treated with 10 mL diethyl ether and the resulting slurry stirred for 30 minutes at room temperature. The mixture was filtered and the solid dried under vacuum for at 60° C. for 15 hours to provide 0.28 gm (88%) of the title compound.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 4 hours
  3. concentrationwas then concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in methanol
  5. washeluting with methanol
  6. additionFractions containing the desired free base
  7. concentrationconcentrated under reduced pressure
  8. washeluting with a gradient of dichloromethane containing 0-6% methanol
  9. additionFractions containing product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a7845bcc47d64bc499cdae9a87b76b56
Source dataset
uspto-grants-2005_04
Patent number
US06881733B1

Reaction notes

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