Synthesis
General procedure for the synthesis of 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-trioxaborolan-2-yl)aniline from 4-(tert-butyloxycarbonylamino)-3-methoxyphenylboronic acid pinacol ester: 4-(tert-butyloxycarbonylamino)-3-methoxyphenylboronic acid pinacol ester (45.0 g, 0.129 mol) was dissolved in dichloromethane (270 mL). It was cooled in an ice bath until the temperature was below 5 °C. Subsequently, a 1:1 trifluoroacetic acid (TFA)/dichloromethane mixture (500 mL) was slowly added, while the reaction temperature was strictly controlled not to exceed 5 °C. Upon completion of the reaction, the mixture was gradually warmed up to room temperature and stirred continuously for 2 hours. At the end of the reaction, the solvent was removed by evaporation under reduced pressure (30 Torr) and a bath temperature of less than 30°C. The residue was re-dissolved in dichloromethane. The residue was redissolved in dichloromethane (250 mL) and washed carefully with 2.5N sodium hydroxide solution (300 mL). After separation of the organic layer, it was extracted with brine (100 mL) and subsequently dried over anhydrous magnesium sulfate, filtered and concentrated to afford the target product 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-trioxaborolan-2-yl)aniline (21.7 g, 68% yield). The product was confirmed by 1H NMR (DMSO-d6, 400MHz): δ 7.05 (d, 1H), 6.98 (d, 1H), 6.59 (d, 1H), 5.13 (s, 2H), 3.75 (s, 3H), 1.25 (s, 12H). Reversed-phase HPLC analysis conditions: Hypersil HS column (5 μm, 100, 4.6 × 250 mm); mobile phase from 0% up to 100% acetonitrile/0.05 M ammonium acetate in 25 min, held for 10 min; flow rate 1 mL/min; retention time 11.03 min.
References
[1] Patent: US2005/20619, 2005, A1. Location in patent: Page 40-41
[2] Patent: US2005/43347, 2005, A1. Location in patent: Page/Page column 49
[3] Patent: US2002/156081, 2002, A1
[4] Patent: US6921763, 2005, B2
