Phenylacetic Acid → 3-{[3-(Methyloxy)phenyl]methyl}-2-phenylpentanoic acid

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Reaction Conditions

Reaction Steps

Phenylacetic acid (0.84 g, 6.07 mmol) was dissolved in THF (50 mL) and cooled in an ice bath. nBuLi (2.5 M in hexanes, 5.4 mL, 13.4 mmol) was added dropwise. The mixture was stirred at 0° C. for 1 h, then at room temperature for 5 h. HMPA (0.25 mL) was added, and the stirring was continued for another 30 min. Cooled in an ice bath, a solution of 3-(2-bromobutyl)phenyl methyl ether (53) (1.77 g, 7.28 mmol) in THF (10 mL) was added dropwise. The resulting mixture was allowed to warm up to room temperature and stir at room temperature overnight, then heated at 50° C. for 1 h. Cooled and quenched with 0.5 N NaOH (25 mL), the mixture was again heated at 50° C. for 1 h. After cooled to room temperature and extracted with ether, the aqueous layer was acidified with 5 N HCl and extracted with CHCl3. The extracts were combined and washed with brine, dried (Na2SO4), filtered, and the filtrate was concentrated to give the crude product as a yellow oil. The crude product was purified by flash chromatography over SiO2 with CH2Cl2:Acetone (8:1) to give 0.81 g (45%) of the title compound (54) as a colorless viscous oil. 1HNMR indicated it was a mixture of two diastereomers with a ratio of 2:1.

Provenance & Evidence