Sulfuric Acid → Pregabalin

HRID 269412Notes

Reaction equation

HRID 269412 reaction equation
S(=O)(=O)(O)O.COC(=O)[NH:9][CH2:10][C@H:11]([CH2:16][C:17](=[O:27])N[C@H](C1C=CC=CC=1)C)[CH2:12][CH:13]([CH3:15])[CH3:14].[OH-:29].[Na+]>>[CH3:15][CH:13]([CH2:12][C@H:11]([CH2:10][NH2:9])[CH2:16][C:17]([OH:27])=[O:29])[CH3:14]

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 59832562Methyl ((S)-4-Methyl-2-[2-oxo-2-[[(S)-1-phenylethyl]amino]ethyl]pentyl]carbamate

Product 1

HCID 5486971PregabalinYield 50.4%

Conditions

Temperature
117.5 °C

Procedure

A 0.2 l reactor was loaded with 70% sulfuric acid (200 g) containing compound 26 (10 g, 0.031 mole), and was heated to 115-120° C. for 5-10 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 50 ml of isopropanol, the organic layer was separated, and NH4OH was added in an amount sufficient to provide a pH of 4. The (S)-Pregabalin was precipitated, filtered, and washed with 10 ml of isobutanol. After drying at 55° C. under vacuum, (S)-Pregabalin was obtained as white crystals in a 50.4% yield. Purity: 99.05% area by HPLC.

Workup

  1. temperaturecooled to room temperature
  2. customi.e., about 20° to about 25° C
  3. customto provide a pH of 1
  4. extractionThe solution was then extracted with 50 ml of isopropanol
  5. customthe organic layer was separated
  6. additionNH4OH 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 isobutanol
  11. customAfter drying at 55° C. under vacuum

Sources & evidence

ORD record
ord-a634d095ebe340c0a11aa592f28b3782
Source dataset
uspto-grants-2008_11
Patent number
US07446220B2

Reaction notes

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