Hydrogen Bromide → Pregabalin

HRID 732295Notes

Reaction equation

HRID 732295 reaction equation
Br.COC(=O)[NH:5][CH2:6][C@H:7]([CH2:12][C:13](=[O:23])N[C@H](C1C=CC=CC=1)C)[CH2:8][CH:9]([CH3:11])[CH3:10].[OH-:25].[Na+]>O>[CH3:11][CH:9]([CH2:8][C@H:7]([CH2:6][NH2:5])[CH2:12][C:13]([OH:23])=[O:25])[CH3:10]

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 14798Sodium HydroxideHCID 59832562Methyl ((S)-4-Methyl-2-[2-oxo-2-[[(S)-1-phenylethyl]amino]ethyl]pentyl]carbamate

Product 1

HCID 5486971PregabalinYield 90%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A flask was loaded with 47% HBr (12 ml), water (6 ml), and compound 26 (6 g), and then was heated to reflux for 3 hours. The solution was cooled to room temperature, and water (12 ml) was added. An aqueous 47% sodium hydroxide solution was added to obtain pH of 3. The solution was then extracted twice with isobutanol (15 ml), the combined organic layers were evaporated and fresh isobutanol was added (15 ml). Bu3N (3.8 g) was added. The mixture was cooled to 2° C. for 1 hour, then (S)-Pregabalin was filtered, and washed with of iso-butanol (3 ml). After drying at 55° C. under vacuum, (S)-Pregabalin was obtained as white crystals in a 90% yield.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 3 hours
  3. customto obtain pH of 3
  4. extractionThe solution was then extracted twice with isobutanol (15 ml)
  5. customthe combined organic layers were evaporated
  6. additionfresh isobutanol was added (15 ml)
  7. additionBu3N (3.8 g) was added
  8. temperatureThe mixture was cooled to 2° C. for 1 hour
  9. filtration(S)-Pregabalin was filtered
  10. washwashed with of iso-butanol (3 ml)
  11. customAfter drying at 55° C. under vacuum

Sources & evidence

ORD record
ord-5cdfb56882594280a8e6d23100488718
Source dataset
uspto-grants-2009_09
Patent number
US07586005B2

Reaction notes

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