Acetic Acid → t-Butyl 2-oxo-4-(4-methylphenyl)-butanoate

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Reaction Steps

To a solution of 4-methylbenzaldehyde (2.5 mL, 21.2 mmol) in 25 mL of benzene was added 1 mL each of acetic acid and piperidine. The mixture was heated to reflux with azeotropic removal of water via a Dean-Stark trap. A solution of t-butyl pyruvate (3.36 g, 23.32 mmol) in 5 mL of benzene was added over 7 h by syringe pump. The mixture was cooled, diluted with ethyl acetate and washed three times with saturated aqueous sodium bicarbonate and three times with 1N hydrochloric acid. The organics were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by MPLC on silica-gel eluting with 2.5% ethyl acetate in hexane to give the desired product as a yellow oil: 1H NMR (200 MHz, CDCl3) δ7.75 (d, 1H, J=16.19 Hz), 7.49 (d, 2H, J=8.25 Hz), 7.24 (m, 3H), 2.37 (s, 3H), 1.58 (s, 9H). The above product was dissolved in ethyl acetate and held under hydrogen in the presence of 100 mg of 10% palladium on carbon for 2 hours. The mixture was filtered and concentrated in vacuo to give 1.196 g of the title compound as a pale-yellow oil: 1H NMR (200 MHz, CDCl3) δ7.1-6.9 (m, 4H), 3.12 (t, 2H, J=6.8 Hz), 2.90 (t, 2H, J=7.3 Hz), 1.56 (s, 9H). ##STR29## N-[1(R)-Benzyloxycarbonyl-5-(1,3-dioxo-isoindolin-2-yl)pentyl]-α-(S)-(2-phenyl-ethyl)!glycine-(L)-leucine, N-phenylamide (5d')

Provenance & Evidence