Methanol → Dexmethylphenidate

HRID 1374130

Reaction equation

HRID 1374130 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C@@H:6]1[NH:11][CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:4].[C:18]1([CH3:45])[C:19]([C:24]([C@:26]([C:42]([OH:44])=[O:43])([OH:41])[C@:27]([C:32]([C:34]2[C:35]([CH3:40])=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:33])([OH:31])[C:28]([OH:30])=[O:29])=[O:25])=[CH:20][CH:21]=[CH:22][CH:23]=1.CO>CC(C)=O>[C:18]1([CH3:45])[C:19]([C:24]([C@:26]([C:42]([O-:44])=[O:43])([OH:41])[C@:27]([C:32]([C:34]2[C:35]([CH3:40])=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:33])([OH:31])[C:28]([O-:30])=[O:29])=[O:25])=[CH:20][CH:21]=[CH:22][CH:23]=1.[CH3:1][O:2][C:3]([C@H:5]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C@@H:6]1[NH:11][CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:4]

Participants

6

Reactant 3

HCID 887MethanolHCID 6101852methyl (S)-phenyl((R)-piperidin-2-yl)acetate2×HCID 129858806(+)-di-toluoyl-D-tartaric acid

Product 2

HCID 154101DexmethylphenidateYield 97%HCID 131722594ditoluoyl-D-tartrate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Resolve dl-threo-methylphenidate by the procedure described in the Example of PCT/GB97/00185 (International Publication No. WO 97/27176): Ditoluoyl-D-tartaric acid (5.033 g, 12.4 mmol) was suspended in a solution of 2% methanol in acetone (10 ml), and a solution of threo-methylphenidate (2.9 g, 12.4 mmol) in the same solvent (10 ml) was added. The solution was gently warmed to reflux whereupon all the reagents dissolved. The solution was immediately cooled and crystals began to form. The solution was allowed to stand at 4° C. for 17 hours and was then filtered. The crystals were washed with acetone (3×15 ml) and dried in vacuc to yield the ditoluoyl-D-tartrate salt of d-threo-methylphenidate (3.516 g, 44.3% by weight; corresponding to 97%. ee d-threo methylphenidate, as determined by chiral HPLC after salt cracking). The mother liquors were dried in vacuo to yield the ditoluoyl-D-tartrate salt of l-threo-methylphenidate as a solid, dry form (4.508 g, 50.5% yield, 88% ee).

Workup

  1. temperatureThe solution was gently warmed
  2. temperatureto reflux whereupon all the reagents
  3. dissolutiondissolved
  4. temperatureThe solution was immediately cooled
  5. customto form
  6. filtrationwas then filtered
  7. washThe crystals were washed with acetone (3×15 ml)
  8. customdried in vacuc

Sources & evidence

ORD record
ord-eb4b30fa4fec40fdb01f055860b52701
Source dataset
uspto-grants-2007_01
Patent number
US07164025B2

Linked notes

Loading…