Benzoic acid,2,4-diMethoxy-6-Methyl-,2- Methylpropyl ester synthesis

Yield:1276019-92-1 89%

Reaction Conditions:

Stage #1: 2-bromo-1,5-dimethoxy-3-methylbenzenewith n-butyllithium in tetrahydrofuran at -78; for 1 h;
Stage #2: isobutyl chloroformate in tetrahydrofuran at -78 - 20; for 2 h;

Steps:

Preparation of compound 7

To a solution of 8 (5.00 g, 21.64 mmol) in THF (40 mL) at -78 °C was added n-BuLi (2.2 M, 11.79 mL, 25.94 mmol) dropwise. After the mixture was stirred at -78 °C for 1 h, isobutyl chloroformate (3.84 g, 28.12 mmol) was added slowly. The reaction mixture was allowed to reach room temperature in 2 h, and the reaction was quenched with a saturated solution of NH₄Cl. THF was removed in vacuo. The reaction mixture was extracted with ethyl acetate (3x30 mL). The organic layers were combined, washed with brine (3x30 mL), dried over anhydrous MgSO₄ and concentrated. The residue was subjected to silica gel chromatographic with petroleum ether/EtOAc (25:1) to give 7 (4.86 g, 89%) as a colorless oil.

References:

Jiang, Cheng-Shi;Zhou, Rong;Gong, Jing-Xu;Chen, Li-Li;Kurtán, Tibor;Shen, Xu;Guo, Yue-Wei [Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,# 4,p. 1171 - 1175] Location in patent:supporting information; experimental part