Dimethylformamide → Tert-butyl 4-formyl-2-methylbenzoate

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-bromo-2-methyl-benzoic acid tert-butyl ester (500 g, 1.8 mol) in tetrahydrofuran (5 L) was added n-butyl lithium (1.6 M solution, 1.4 L, 2.2 mol) at such a rate that the reaction temperature is between −95° C. to −100° C. After completion of the addition, the reaction mixture was stirred for 30 min at −100° C. and monitored by quenching the reaction mixture with water and following the product by TLC. After complete conversion, DMF (170 ml, 2.2 mol) was added to the reaction mixture and after 15 min the reaction mixture was quenched with ammonium chloride (sat. solution, 5 L). The organic layers were separated at room temperature and the aqueous layer was extracted with ethyl acetate (3×2 L). The combined organic layer was washed with water (3×5 L), dried over sodium sulphate and concentrated to yield tert-butyl 4-formyl-2-methyl-benzoate (390 g, 96% isolated yield, 75-78% HPLC purity). The crude product was used as such without any further purification for the next step. 1H-NMR (CDCl3, 400 MHz): δ in ppm=1.59 (s, 9 H), 2.61 (s, 3 H), 7.71 (d, 2 H), 7.92 (d, 1 H), 10.01 (s, 1 H).

Provenance & Evidence