Acetone → 3,3-Dimethyl-1,3-dihydro-2,1-benzoxaborol-1-ol

Temperature

-78 °C

To a solution of 2-(2′-bromophenyl)-6-butyl[1,3,6,2]dioxazaborocan (93.1 g, 277.1 mmol) in THF (2.3 L) at −78° C. was added n-BuLi (133.0 mL, 2.5M in hexane, 332.5 mmol, 1.2 equiv.) dropwise via a syringe over a period of 10 min while maintaining reaction temperature at −78° C. After the addition the reaction solution was stirred for 20 min at −78° C. before acetone (23.2 mL, 387.9 mmol, 1.4 equiv.) was added dropwise via a syringe over a period of 10 min while maintaining the reaction temperature at −78° C. The resulting mixture was allowed to stir for 20 min at −78° C. then warm to room temperature gradually. Once the reaction vessel reached room temperature, 6N HCl solution (1 L) was added and the mixture was stirred for an additional 30 min. The mixture was extracted with EtOAc (3×). The EtOAc extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. The light yellow oil was then subjected to flash chromatography (Isco Companion, 80 g SiO2 cartridge, solid loaded SiO2, neat heptanes to 20:80 EtOAc gradient at 60 ml/min for 90 min). The title compound was recovered as clear colorless oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44 (s, 6 H) 7.31 (d, J=1.1 Hz, 1 H) 7.38-7.47 (m, 2 H) 7.66 (d, J=7.2 Hz, 1 H) 8.99 (s, 1 H). Amount obtained: 16.9 g (37.7% yield).

1. temperaturewhile maintaining
2. customreaction temperature at −78° C
3. additionAfter the addition the reaction solution
4. additionwas added dropwise via a syringe over a period of 10 min
5. temperaturethen warm to room temperature gradually
6. customreached room temperature
7. stirringthe mixture was stirred for an additional 30 min
8. extractionThe mixture was extracted with EtOAc (3×)
9. dry with materialThe EtOAc extracts were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customwas then subjected to flash chromatography (Isco Companion, 80 g SiO2 cartridge, solid loaded SiO2, neat heptanes to 20:80 EtOAc gradient at 60 ml/min for 90 min)
13. customThe title compound was recovered as clear colorless oil
14. customAmount obtained

ORD record

ord-bff9de13c1824a4fbceecc93c7677ef4

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440994B2