Methyl iodide → 4-Tert-butyl-2-methylbenzoic acid

Participants

Reaction Steps

A 250 mL round bottom flask was charged with tetramethylethylene diamine (5.6 mL, 37 mmol) in THF (34 mL). After the mixture was cooled to −92° C. (N2(liq)/CH2Cl2 bath), sec-BuLi (26.5 mL, 37 mmol, 1.4M solution in cyclohexane) was added, followed by the dropwise addition of a solution of 4-tert-butylbenzoic acid (3 g, 16.8 mmol) dissolved in THF (22 mL). After stirring for 1 h, methyliodide (4.5 mL, 72.4 mmol) was added to mixture at −80° C. After stirring for 10 min at −80° C., the reaction mixture was quenched H2O (20 mL). Upon warming to room temperature, the aqueous phase adjusted to pH=2 with aqueous HCl (1M). The aqueous phase was extracted with EtOAc (2×15 mL), and the combined organic extracts were dried with Na2SO4 and concentrated. The residue was chromatographed with (gradient, 10%-60% EtOAc/hexanes) to afford 630 mg (20%) 101a.

Provenance & Evidence