Sodium Hydroxide → Pregabalin

HRID 732292Notes

Reaction equation

HRID 732292 reaction equation
COC(=O)[NH:4][CH2:5][C@H:6]([CH2:11][C:12](=[O:14])N)[CH2:7][CH:8]([CH3:10])[CH3:9].[OH-:16].[Na+]>Cl>[CH3:9][CH:8]([CH2:7][C@H:6]([CH2:5][NH2:4])[CH2:11][C:12]([OH:14])=[O:16])[CH3:10]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59832564{(S)-2-carbamoylmethyl-4-methylpentyl)carbamic acid methyl ester

Product 1

HCID 5486971PregabalinYield 21.5%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A 0.2 l reactor was loaded with 6N hydrochloric acid (100 ml) containing compound 27 (12 g, 0.055 mole), and was heated to 100°-110° C. for 12-24 hours, and then cooled to room temperature, i.e., about 20° to about 25° C. An aqueous 40% sodium hydroxide solution was added in an amount sufficient to provide a pH of 1. The solution was then extracted with 37 ml of iso-butanol, the organic layer was separated, and Bu3N was added in an amount sufficient to provide a pH of 4. The (S)-Pregabalin was precipitated, filtered, and washed with 10 ml of iso-butanol. After drying at 55° C. under vacuum, (S)-Pregabalin was obtained as white crystals in a 21.5% yield. Purity: 99.9% area by HPLC.

Workup

  1. temperaturewas heated to 100°-110° C. for 12-24 hours
  2. customi.e., about 20° to about 25° C
  3. customto provide a pH of 1
  4. extractionThe solution was then extracted with 37 ml of iso-butanol
  5. customthe organic layer was separated
  6. additionBu3N was added in an amount sufficient
  7. customto provide a pH of 4
  8. customThe (S)-Pregabalin was precipitated
  9. filtrationfiltered
  10. washwashed with 10 ml of iso-butanol
  11. customAfter drying at 55° C. under vacuum

Sources & evidence

ORD record
ord-c0804ddd40444bd180ef0b41c1c3c668
Source dataset
uspto-grants-2009_09
Patent number
US07586005B2

Reaction notes

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