Toluene → Methyl 4-cyclopropyl-2-methylbenzoate

Participants

Reaction Steps

Cyclopropylboronic acid (25.08 g, 292 mmol), anhydrous tribasic potassium phosphate (178.12 g, 839 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.925 g, 14.5 mmol), methyl 4-bromo-2-methylbenzoate (55.93 g, 244 mmol), and 600 mL of toluene were charged into a 1000 mL round bottom flask fitted with a stir bar, septum, and nitrogen inlet. Stirred the mixture rapidly and added 65 mL of water. Sparged the mixture with nitrogen for 30 min. Added tris(dibenzylideneacetone)dipalladium(0) (3.321 g, 3.63 mmol). The reaction mixture was sparged with nitrogen for 15 min. Sealed the flask with a cap and stirred at 90° overnight. Added 150 mL water and allowed to cool to room temperature. Filtered the two phase system through diatomaceous earth to remove the solids and washed the filter cake with EtOAc. Separated the filtrate phases and washed the organic phase with 2×200 mL 5% NaHCO3, 2×200 mL 10% Na2S2O3, and 200 mL brine. Dried the solution over MgSO4 and concentrated in vacuo. Vacuum distilled the residual liquid. Collected the fraction distilling at 108-111°/3 torr to obtain methyl 4-cyclopropyl-2-methylbenzoate as a clear colorless liquid (32.30 g, 170 mmol). 1H NMR (300 MHz, chloroform-d) ppm 0.71-0.80 (m, 2H) 0.98-1.07 (m, 2H) 1.83-1.95 (m, 1H) 2.58 (s, 3H) 3.87 (s, 3H) 6.87-6.96 (m, 2H) 7.83 (d, J=7.91 Hz, 1H).

Provenance & Evidence