Sulfuric Acid → Ibuprofen methyl ester
Reaction equation
C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.[CH2:16]([C:20]1[CH:25]=[CH:24][C:23]([C:26](=O)[CH2:27]C)=[CH:22][CH:21]=1)[CH:17]([CH3:19])[CH3:18].[CH3:30][O:31][CH:32](OC)[O:33]C.S(=O)(=O)(O)O>>[CH3:30][O:31][C:32]([CH:26]([C:23]1[CH:22]=[CH:21][C:20]([CH2:16][CH:17]([CH3:18])[CH3:19])=[CH:25][CH:24]=1)[CH3:27])=[O:33]Participants
Procedure
To a suspension of iodobenzene diacetate (322 grams(g), 1.0 mol) in a solution of p-isobutylpropiophenone (190 g, 1.0 mol) in trimethylorthoformate (109 ml, 1.0 mol) was added, dropwise, concentrated sulfuric acid (about 96% H2SO4, 10.7 ml, 0.2 mol) at 3° C. with stirring over 40 minutes. The resulting reaction mixture was stirred 6 hours at 0° C. to 15° C. The ensuing reaction was quenched by adding 200 ml deionized water. HPLC (high performance liquid chromatography) analysis of the resulting reaction product, comparing to an external standard, demonstrated 79% yield of ibuprofen methylester. The mixture obtained can be separated into an aqueous phase and an organic phase, followed by isolation of purified ibuprofen methyl ester from the organic phase by column chromatography or distillation. Alternatively, the crude ester can be hydrolyzed by treating with 50% aqueous sodium hydroxide, followed by extraction of the resulting aqueous phase with heptane. Acidification of the aqueous phase and recrystallization of the solid precipitate yields high-purity ibuprofen.
Workup
- additionwas added
- customThe resulting reaction mixture
- customThe ensuing reaction
- customwas quenched
- additionby adding 200 ml
- customHPLC (high performance liquid chromatography) analysis of the resulting reaction product
Sources & evidence
- ORD record
- ord-f74b2420b53448ab9a5b9ca83f449b88
- Source dataset
- uspto-grants-1989_06
- Patent number
- US04843169
Reaction notes
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