Hydrochloric Acid → Focalin

HRID 599389

Reaction equation

HRID 599389 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].[ClH:18]>C(O)(C)C.CO>[CH3:1][O:2][C:3]([C@@H:5]([C@@H:6]1[NH:11][CH2:10][CH2:9][CH2:8][CH2:7]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:4].[ClH:18]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 154101Dexmethylphenidate

Product 1

HCID 154100FocalinYield 86%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3776IsopropanolSolvent2×

Conditions

Temperature
7.5 °C

Procedure

The organic layer was dewatered by azeotropic distillation under vacuum and was concentrated in vacuum to give D-threo-methylphenidate free base as an oil, which was used directly in hydrochloride salt formation. The solution of D-threo-methylphenidate free base in isopropanol (0.29 Kg) was charged to a jacketed vessel, cooled to 5-10° C. and treated with a solution of 37% HCl (78 g) in a mixture of isopropanol (40 g) and methanol (63 g) at less than 20° C. The formed slurry was cooled to 0 to 5° C., aged for 2 hours and filtered. The wet cake was washed with isopropanol (0.32 Kg total) in two portions and dried under vacuum at 45° C. for 16 hours to give Dexmethylphenidate hydrochloride (0.175 Kg, 0.649 mol, 86% yield) as a off-white solid; mp 206.4° C., ee 99.7%, α25D +83° (c 1 wt %, MeOH).

Workup

  1. temperatureThe formed slurry was cooled to 0 to 5° C.
  2. filtrationfiltered
  3. washThe wet cake was washed with isopropanol (0.32 Kg total) in two portions
  4. customdried under vacuum at 45° C. for 16 hours

Sources & evidence

ORD record
ord-ed253010351a4d048e21b0b089654b1e
Source dataset
uspto-grants-2011_03
Patent number
US07897777B2

Linked notes

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