Triisopropyl borate → (4-Methoxy-2,5-dimethylphenyl)boronic acid

Temperature

-62.5 °C

A solution of 4-bromo-2,5-dimethylanisole (5, 172 g, 0.8 mol) in anhydrous THF (800 ml) was treated dropwise with a solution of n-butyl lithium (2.5 M solution in hexane, 352 mL, 0.88 mol, 1.1 equiv) in hexane at −60-−65° C. under N2. The resulting reaction mixture was stired at −60-65° C. for an additional 30 min before being treated dropwise with B(OiPr)3 (165.44 g, 203.2 mL, 0.88 mol, 1.1 equiv) at −60 to −65° C. The reaction mixture was stirred at −60 to −65° C. for an additional 1 h. The reaction was then quenched with saturated NH4Cl aqueous solution (750 mL) at −60 to −65° C., and the resulting mixture was gradually warmed to 0° C. for 1 h and subsequently to room temperature. The two layers were separated, and the aqueous layer was extracted with EtOAc/THF (1:1, 400 mL). The combined organic extracts were then washed with H2O (400 mL), and saturated NaCl solution (400 mL), dried over MgSO4, and concentrated in vacuo. The residual white solids were then suspended in heptane (500 mL), and the resulting suspension was stirred at room temperature for 30 min. The solids were collected by filtration and washed with heptane (2×200 mL), dried in vacuo at 40-45° C. for overnight. The crude product (6, 116.7 g, 144.0 g theoretical, 81%) was obtained as a white powder.

1. customThe resulting reaction mixture
2. customThe reaction was then quenched with saturated NH4Cl aqueous solution (750 mL) at −60 to −65° C.
3. temperaturethe resulting mixture was gradually warmed to 0° C. for 1 h and subsequently to room temperature
4. customThe two layers were separated
5. extractionthe aqueous layer was extracted with EtOAc/THF (1:1, 400 mL)
6. washThe combined organic extracts were then washed with H2O (400 mL), and saturated NaCl solution (400 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. stirringthe resulting suspension was stirred at room temperature for 30 min
10. filtrationThe solids were collected by filtration
11. washwashed with heptane (2×200 mL)
12. customdried in vacuo at 40-45° C. for overnight

ORD record

ord-8c4a163f15884cf2877aa8578792bb36

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06727360B2