2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → 2-(4-Chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Temperature

-10 °C

To a stirred solution of 1-bromo-4-chloro-2-fluoro-3-methoxybenzene (3 g, 12.53 mmol) in tetrahydrofuran (20 mL) cooled to −10° C. was added isopropylmagnesium bromide (5.18 mL, 15.03 mmol) dropwise and the reaction mixture was stirred at −10° C. for 1 h. The reaction mixture was then warmed to 0° C. and stirred for 1 h. The reaction was then cooled to −10° C. and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.56 mL, 12.53 mmol) was slowly added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 16 h. The reaction mixture was quenched with 5% aqueous sodium hydroxide and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with brine solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.3 g, 8.03 mmol, 64% crude yield) as a brown oil. The material was carried forward without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 7.35 (m, 1H), 7.15 (m, 1H), 3.95 (s, 3H), 1.33 (s, 6H), 1.23 (s, 6H).

1. temperatureThe reaction mixture was then warmed to 0° C.
2. stirringstirred for 1 h
3. temperatureThe reaction was then cooled to −10° C.
4. temperatureto warm to room temperature
5. stirringstirred for 16 h
6. customThe reaction mixture was quenched with 5% aqueous sodium hydroxide
7. extractionextracted with ethyl acetate (2×25 mL)
8. washThe combined organic layers were washed with brine solution
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure

ORD record

ord-d779608311374a88ab071038dd7e5be3

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901305B2