2-Bromopropionic acid → Ibuprofen, (+-)-

HRID 1388808Notes

Reaction equation

HRID 1388808 reaction equation
Br[CH:2]([CH3:6])[C:3]([OH:5])=[O:4].[CH2:7]([C:11]1[CH:16]=[CH:15][C:14]([Mg]Br)=[CH:13][CH:12]=1)[CH:8]([CH3:10])[CH3:9]>C1COCC1>[CH2:7]([C:11]1[CH:16]=[CH:15][C:14]([CH:2]([CH3:6])[C:3]([OH:5])=[O:4])=[CH:13][CH:12]=1)[CH:8]([CH3:10])[CH3:9]

Participants

4

Reactant 2

HCID 117292-Bromopropionic acidHCID 178440987HCID 178440987, compound

Product 1

HCID 3672Ibuprofen, (+-)-Yield 21.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
50 °C

Procedure

67 ml of a 1.5 M solution of a mixed magnesium chloride complex of α-bromopropionic acid in THF was slowly added to 67 ml of a 1.5 M solution cooled to 10° C. of p-isobutylphenyl magnesium bromide in THF at such a rate that the temperature of the mixture was maintained at not more than 55° C. The resulting slurry was stirred at 50° C. for 1 hour, and then heated under reflux to allow about 50% of THF to distill. The reaction mixture was cooled, and diethyl ether and dilute hydrochloric acid were added. The organic layer was washed with water, dried, concentrated, and purified by silica gel column chromatography to give 4.4 g (yield 21.3%) of α-(p-isobutylphenyl)propionic acid.

Workup

  1. temperaturewas maintained at not more than 55° C
  2. temperatureheated
  3. temperatureunder reflux
  4. distillationto distill
  5. temperatureThe reaction mixture was cooled
  6. additiondiethyl ether and dilute hydrochloric acid were added
  7. washThe organic layer was washed with water
  8. customdried
  9. concentrationconcentrated
  10. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-96bb925db2ea4c39901f5d53e7986c09
Source dataset
uspto-grants-1984_02
Patent number
US04433160

Reaction notes

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