Hydrochloric Acid → tert-Butyl (R)-6-Cyano-5-hydroxy-3-oxohexanoate

Participants

Reaction Steps

To a stirred -50° C. solution of lithium diisopropylamide (100 kg of 2 M) in tetrahydrofuranheptane is added tertiary-butyl acetate (30 kg, 255 mol) followed by a rinse of 3 kg of tetrahydrofuran and the mixture is stirred at -45° C. to -5° C. for 50 minutes. (R)-4-cyano-3-hydroxybutyric acid, ethyl ester (10 kg, 64 mol) as a solution in 30 kg of tetrahydrofuran is then added to the previous mixture. The reaction mixture is stirred for 30 minutes at -5° C. to -30° C., and transferred to 240 L of 0° C. 2.8 N aqueous hydrochloric acid solution. The aqueous layer is extracted with 50 kg of ethyl acetate, the aqueous layer is separated and reextracted with 36 kg of ethyl acetate, the extracts are combined and concentrated in vacuo to afford crude (5R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxo -hexanoate which is not isolated. A small sample is purified by column chromatography on flash silica gel eluting with 1:1 hexane:ethyl acetate. 1H--NMR: (CDCl3) 1.48 (9H, s), 2.61 (2H, m), 2.88 (2H, d), 3.43 (2H, s), 3.58 (1H, bs), 4.40 (1H, m). MS:(EI) m/e, (%): 229 (3), 228(26),173(10), 172(100), 154(62), 112(30), 59(50), 57(77).

Provenance & Evidence