(-)-Mandelic acid → (s)-(+)-3-(4-Fluorobenzyl)piperidine mandelic acid salt

HRID 1766402Notes

Reaction equation

HRID 1766402 reaction equation
[F:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][CH:7]2[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)=[CH:4][CH:3]=1.[C:15]([OH:25])(=[O:24])[C@@H:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[OH:17]>C(#N)C>[C:15]([OH:25])(=[O:24])[CH:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[OH:17].[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C@@H:7]2[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)=[CH:13][CH:14]=1

Participants

4

Reactant 2

HCID 11914(-)-Mandelic acidHCID 34323433-(4-Fluorobenzyl)piperidine

Product 1

HCID 69358447(s)-(+)-3-(4-Fluorobenzyl)piperidine mandelic acid salt

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

The crude racemic 3-(4-fluorobenzyl)piperidine (2.0 g) was dissolved in 25 mL acetonitrile and heated to reflux. The solution was hazy. To this was added 1.56 g (1 equivalent) of (R)-(−) mandelic acid dissolved in 15 mL acetonitrile. Some initial precipitation occurred when the cooler solution was added but it redissolved when refluxing resumed. The heat was turned off and small amounts of enantiomerically pure salt were added as the temperature dropped. At first the seed crystals dissolved, but when the temperature dropped to 75° C., they remained suspended in the stirred solution. After a few more degrees of cooling, crystal growth was obvious. Cooling was continued at the rate of 1 degree/min. At 50° C., the solution was filtered to recover 0.9 g of salt, which melted at 164° C. It was recrystallized from acetonitrile twice to give (S)-(+)-3-(4-fluorobenzyl)piperidine mandelic acid salt in 98% enantiomeric excess, mp 168-171° C.

Workup

  1. temperatureheated to reflux
  2. customSome initial precipitation
  3. additionwas added
  4. dissolutionit redissolved when
  5. temperaturerefluxing
  6. additionsmall amounts of enantiomerically pure salt were added as the temperature
  7. additiondropped
  8. dissolutionAt first the seed crystals dissolved
  9. additionwhen the temperature dropped to 75° C.
  10. temperatureAfter a few more degrees of cooling
  11. temperatureCooling
  12. filtrationAt 50° C., the solution was filtered
  13. customto recover 0.9 g of salt, which melted at 164° C
  14. customIt was recrystallized from acetonitrile twice

Sources & evidence

ORD record
ord-53b71c913a2f4042805ca6b348f700e8
Source dataset
uspto-grants-2007_06
Patent number
US07230022B2

Reaction notes

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