Toluene → 3-(3,4-Di-chlorophenyl)-4-pentenoic acid

Participants

Reaction Conditions

Reaction Steps

Treat a solution of the product of Step 3 (15 g, 61 mmol, dried by azeotropic distillation with toluene, 1×50 mL) in dry THF (250 mL) at -78° C. with chlorotriethylsilane (20.2 mL, 120 mmol), rapidly followed by the addition of 0.5M toluene solution of potassium bis(trimethylsilyl)amide (183 mL, 91.5 mmol) via addition funnel over 50 min. Allow the mixture to warm to 23° C., then heat to reflux for 3 h. Allow the solution to gradually cool overnight, then quench with saturated NH4Cl (150 mL). Stir the resulting mixture vigorously for 3 h, treat with 1M HCl (150 mL) and extract with Et2O (500 mL). Extract the aqueous layer with Et2O (400 mL) and wash the combined organic layers with 300 mL of 5% NaOH followed by 8×150 mL of 5% NaOH. Cool the combined aqueous layers to 5° C. and carefully (temperature kept to 5°-10° C.) acidify with conc. HCl (ca 175 mL) to pH 1. Extract the aqueous layer with CH2Cl2 (2×800 mL), dry (Na2SO4) and concentrate to give 3-(3,4-di-chlorophenyl)-4-pentenoic acid as a faint yellow oil, 13.4 g (54.5 mmol, 89%).

Provenance & Evidence