CID 406 → Dimethyl (3-cyclohexyl-2-oxopropyl)phosphonate

Participants

Reaction Steps

A solution of 49.6 g (0.40 mole) dimethyl methylphosphonate (Aldrich) in 500 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 188 ml of 2.34 M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 40 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 31.2 g (0.20 mole) methylcyclohexylacetate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 1.0 hour at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 25 ml acetic acid and rotary evaporated to a white gel. The gelatenous material was taken up in 75 ml water, the aqueous phase extracted with 100 ml portions of chloroform (3x), the combined organic extracts were backwashed (50 cc H 2 O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 160°-162° (0.2 mm) to give dimethyl 2-oxo-3-cyclohexylpropylphosphonate (2h).

Provenance & Evidence