Hydrochloric Acid → methyl (S)-phenyl((R)-piperidin-2-yl)acetate

HRID 1275803

Reaktionsgleichung

Reaktionsgleichung von HRID 1275803
[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].Cl.C1C=C2C=CC3OP(O)(=O)OC4C=CC5C(C=4C=3C2=CC=1)=CC=CC=5.Cl>>[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]

Komponenten

4

Edukt 3

HCID 313Hydrochloric AcidHCID 99589(+-)-1,1'-Binaphthyl-2,2'-diyl hydrogen phosphate2×HCID 45259401L-threo-Methylphenidate hydrochloride

Produkt 1

HCID 6101852methyl (S)-phenyl((R)-piperidin-2-yl)acetate

Versuchsvorschrift

As alluded to above, racemic threo methylphenidate hydrochloride is known and commercially available, as is the resolving agent employed in Steps 2 and 1A, viz., (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate. In the latter connection, another advantage of the process of the invention is that the resolving agent is recyclable. Thus, the (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate may be recovered by: 1) combining the sodium salt thereof obtained by basifying the filtrate from Step 2, collecting the solid by filtration, and extracting the solid with isopropyl acetate, with the sodium salt and aqueous layer obtained in Step 3; 2) allowing the mixture to react at reflux temperature for between 30 and 45 minutes; and 3) treating the mixture with concentrated hydrochloric acid, initially at the reflux temperature for between 30 and 60 minutes, and then at a temperature of between 15° and 30° C. for a period of between 3 and 5 hours. The recovered (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate is of comparable purity to that of the commercially available material. A resolution of the free base form of racemic threo methylphenidate with the recovered material yielded the desired phosphate salt enriched with the d-threo isomer of methylphenidate.

Aufarbeitung

  1. customThus, the (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate may be recovered by: 1)
  2. customthereof obtained
  3. customcollecting the solid
  4. filtrationby filtration
  5. extractionextracting the solid with isopropyl acetate
  6. customto react
  7. temperatureat reflux temperature for between 30 and 45 minutes
  8. waitinitially at the reflux temperature for between 30 and 60 minutes
  9. waitat a temperature of between 15° and 30° C. for a period of between 3 and 5 hours

Quellen und Nachweise

ORD-Eintrag
ord-3d82d5de8f454801aed05393d91f6fac
Quelldatensatz
uspto-grants-2000_12
Patentnummer
US06162919

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