Tetrahydrofuran → 4-Phenylbutyric Acid

Participants

Reaction Conditions

Reaction Steps

A solution of 4-phenyl-butyric acid methyl ester (compound of example 47) (5 g, 28.05 mmol) in anhydrous THF (200 mL) was prepared and cooled to −78° C. To this solution was added by cannula a freshly prepared solution of LDA (28.05 mmol, ca. 1M) in anhydrous THF. The reaction mixture was stirred for 30 minutes, then treated drop wise with a cooled solution of tert-butyl bromoacetate (4.6 mL, 30.86 mmol) in anhydrous THF (30 mL). HMPA (1.2 mL) was added and stirring was continued at −78° C. for an additional 30 minutes followed by slowly warming to room temperature. Stirring was continued overnight. Saturated ammonium chloride was added and after stirring, the organic phase was separated. The aqueous phase was extracted several times with ethyl acetate. The recombined organic layer was washed with brine, dried over sodium sulfate and filtered. The solvent was evaporated and the crude product was flashed using 10% ethyl acetate in hexanes. Based on its 1H NMR spectrum, the flashed oily colorless product was considered sufficiently pure for the next step. 1H-NMR(CDCl3, 300 MHz: 1.43(s, 9H); 1.99(m, 2H); 2.40(m, 1H); 2.73(m, 4H); 2.84(m, 1H); 3.71(s, 3H); 7.21(m, 5H).

Provenance & Evidence