Acetyl chloride → 2-(4-Chloro-2-fluoro-3-methoxyphenyl)-1,3,2-dioxaborinane

Temperature

0 °C

To a solution of 1-bromo-4-chloro-2-fluoro-3-methoxybenzene (10.4 g, 0.043 mol) in diethyl ether (150 mL) at −78° C. was slowly added n-butyl lithium (2.5M, 19.0 mL, 0.0475 mol) and the solution was stirred for 30 minutes. A solution of triisopropyl borate (12.0 g, 0.064 ml) in THF (25 mL) was slowly added and the solution was warmed to a 0° C. Acetyl chloride (10.0 g, 0.13 mol) was added. After stirring for 1 hour, the solution was concentrated and the solid residue taken into ethyl acetate (150 mL) and a 1N solution of sodium hydroxide (50 mL). Ice was added to the aqueous phase which was then acidified with sufficient concentrated hydrochloric acid to obtain a pH of 2. The heterogeneous mixture was extracted with ethyl acetate (2×150 mL) and the combined organic phases dried (sodium sulfate) and concentrated. The resulting solid was slurried in toluene and propane-1,3-diol (6.6 g, 0.09 mol) was added and the mixture heated under reflux with water being removed with a Dean-Stark trap. After 2 hours the mixture was cooled and concentrated. The resulting oil was taken into methylene chloride (50 mL) and washed with water (25 mL), then dried (sodium sulfate) and concentrated to give 2-(4-chloro-2-fluoro-3-methoxyphenyl)-[1,3,2]-dioxaborinane (6.4 g, 0.062 mol): 1H NMR (CDCl3): δ 7.15 (m, 1H), 6.95 (dd, 1H), 4.05 (t, 4H), 3.8 (s, 3H), 1.95 (t, 2H).

1. customat −78° C.
2. stirringAfter stirring for 1 hour
3. concentrationthe solution was concentrated
4. additionIce was added to the aqueous phase which
5. customto obtain a pH of 2
6. extractionThe heterogeneous mixture was extracted with ethyl acetate (2×150 mL)
7. dry with materialthe combined organic phases dried (sodium sulfate)
8. concentrationconcentrated
9. temperaturethe mixture heated
10. customremoved with a Dean-Stark trap
11. temperatureAfter 2 hours the mixture was cooled
12. concentrationconcentrated
13. washwashed with water (25 mL)
14. dry with materialdried (sodium sulfate)
15. concentrationconcentrated

ORD record

ord-1178bee942944d60a6bc9da8a0f5d29c

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07314849B2