Sodium Hydroxide → Pregabalin

HRID 2423332Notes

Reaction equation

HRID 2423332 reaction equation
COC(=O)[NH:4][CH2:5][C@H:6]([CH2:11][C:12](=[O:22])N[C@H](C1C=CC=CC=1)C)[CH2:7][CH:8]([CH3:10])[CH3:9].[OH-:24].[Na+]>>[CH3:10][CH:8]([CH2:7][C@H:6]([CH2:5][NH2:4])[CH2:11][C:12]([OH:22])=[O:24])[CH3:9]

Participants

3

Reactant 2

HCID 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 1 reactor was loaded with 70% sulfiric 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-adfd7972c3da4ebf8394f8639c5520bb
Source dataset
uspto-grants-2011_06
Patent number
US07960583B2

Reaction notes

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