5-Methoxy-2-methyl-isophthalic acid synthesis

Yield:13979-74-3 93%

Reaction Conditions:

with (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride;triethylamine at 100; under 6000.6 Torr; for 40 h;Sealed tube;

Steps:

2 Step 2: dimethyl 5-methoxy-2-methylbenzene-1,3-dicarboxylate

A mixture of 1,3-dibromo-5-methoxy-2-methylbenzene (7a) (12.3 g, 43.9 mmol), PdCI₂(dppf) (2.01 g, 2.75 mmol) and TEA (13.3 g, 132 mmol) in MeOH (350 ml_, c = 0.13 M) was sealed under an atmosphere of CO (0.8 MPa) and stirred at 100 °C for 40 h. TLC analysis (petroleum ether) indicated consumption of the starting material. The reaction mixture was combined with a parallel reaction conducted with 900 mg 1,3-dibromo-5-methoxy-2-methylbenzene. The mixture was filtered. The filter cake was washed with MeOH (3x10 mL). The filtrate was concentrated to dryness to provide a red solid. The residue was purified by flash chromatography (Isco, 120 g S1O2, petroleum ether/EtOAc = 6:1) to provide dimethyl 5-methoxy- 2-methylbenzene-1,3-dicarboxylate (10.5 g, 93% yield) as a colorless oil. ¹H NMR (400 MHz, CDC) d 7.41 (s, 2H), 3.94 - 3.88 (m, 6H), 3.83 (s, 3H), 2.59 (s, 3H).

References:

WO2021/224818,2021,A1 Location in patent:Page/Page column 46-47