Synthesis
The general procedure for the synthesis of 5-chloro-2-methoxyphenylboronic acid from trimethyl borate and 2-bromo-4-chloroanisole is as follows: 5-chloro-2-methoxyphenylboronic acid (Structure 37 of Scheme XI, wherein R1 = H, R2 = Cl) was prepared in a similar manner to 5-fluoro-2-methoxyphenylboronic acid (Example 107). This was done as follows: in a dry reaction flask, 2-bromo-4-chloroanisole (2.00 g, 9.0 mmol, 1.0 eq.) was added, cooled to -78°C under anhydrous and oxygen-free conditions, n-butyllithium (2.5 M hexane solution, 3.62 mL, 9.0 mmol, 1.0 eq.) was slowly added and the reaction was stirred for 30 minutes. Subsequently, trimethyl borate (3.0 mL, 26 mmol, 2.9 eq.) was added dropwise and the reaction was continued at -78°C for 2 hours. After completion of the reaction, it was slowly warmed to room temperature, the reaction was quenched with water, extracted with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford 1.30 g (77% yield) of crude 5-chloro-2-methoxyphenylboronic acid as a white semi-solid. The compound did not require further purification and could be used directly in the next step of the reaction. Next, the crude 5-chloro-2-methoxyphenylboronic acid was used for the synthesis of methyl (5'-chloro-2'-methoxy-4-nitro-2-biphenylyl) carboxylate (Structure 39 of Scheme XI, where R1 = H, R2 = Cl).
References
[1] Patent: US5688808, 1997, A
[2] Patent: US5688810, 1997, A
[3] Patent: US5693646, 1997, A
[4] Patent: US5693647, 1997, A
[5] Patent: US5696127, 1997, A
