Ammonium Chloride → Ethyl 5(R)-hydroxyhexanoate

Participants

Reaction Conditions

Reaction Steps

A 250 mL, round bottom flask was equipped with a magnetic stirrer, a N2 inlet, a type-J teflon covered thermocouple, and charged with 6 g of (S)-methyl-CBS-borane complex 2 (20.6 mmol) dissolved in 40 mL of dichloromethane (DCM). The solution was cooled to −40° C. before ethyl 4-acetylbutyrate (3 g, 18.9 mmol) in 5 mL of DCM was added dropwise at a rate which kept the internal temperature below −20° C. At the end of addition, the dry ice/isopropanol cooling bath was substituted with an ice bath maintaining the internal reaction temperature at 0° C. for an additional hour. G.C. analysis showed less than 5% starting ketone. The reaction was worked up after 2 h at 0° C. by cautious addition of saturated aqueous ammonium chloride (100 mL). The mixture was transferred to a reparatory funnel and extracted with ethyl acetate (2×100 mL). The separated combined organic extracts were washed with brine and dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to yield 7 g of crude products. Flash column chromatography (FCC) on 120 g of flash grade silica gel eluting with 20% EtOAc-hexanes yielded 1.94 g (65%) of alcohol 3 as an oil. G.C. analysis indicated a purity of 97.4 A %. 1H NMR (CDCl3): 1.20 (d, J=3 Hz, 3H), 1.26 (t, J=7.2 Hz, 3H), 1.47 (m, 2H), 1.71 (m, 3H), 2.34 (t, J=7.5 Hz, 2H), 3.89 (m, 1H), 4.13 (q, J=7.2 Hz, 2H).

Provenance & Evidence