Methyl iodide → HCID 23520304, compound

Participants

Reaction Steps

To mono t-butyl 2-(R)-(n-butyl)succinic acid (2.0 g, 8.70 mmol; prepared in three steps from hexanoylchloride using the procedure of Example 16, Step A for the synthesis of monomethyl-2-R-butylsuccinic acid, with substitution of t-butyl bromoacetate for methyl bromoacetate) in anhydrous THF (40 mL) at −78° C. was added LDA (2.2 eq., 19.1 mmol, 9.56 ml of a 2.0 M solution in THF/hexane/ethyl-benzene) and the reaction stirred for 1 h. Iodomethane (11.3 mmol, 1.6 g) was then added and the reaction allowed to warm to room temperature over 2 h. The solution was quenched with methanol (ca. 5 mL), evaporated to dryness, and the residue dissolved in ethylacetate (50 mL). This solution was extracted with saturated sodium bicarbonate (3×30 mL), the combined aqueous layers acidified to pH 3 with 1 N HCl, and these were extracted with ethylacetate (3×50 mL). The combined organic layers were dried (Na2SO4), concentrated, and purified by silica gel chromatography (Merck 60; 95:5 DCM/methanol) to afford mono t-butyl 2-(R)-(n-butyl)-3-(RS)-methylsuccinic acid as a light orange oil (1.25 g). The ratio of R/S diastereomers was >6:1.

Provenance & Evidence