Triisopropyl borate → 6-Fluorobenzo[c][1,2]oxaborole-1,5(3H)-diol

温度

-78 °C

A solution of 2-(4-bromo-2-fluoro-5-((tetrahydro-2H-pyran-2-yloxy)methyl)phenoxy)tetrahydro-2H-pyran (6.31 g, 16.2 mmol) in anhydrous THF (13.5 mL) was made before cooling the reaction mixture in a −78° C. bath. Reaction mixture was then treated, drop-wise, with n-BuLi (12.15 mL, 19.45 mmol) and allowed to stir for 1.0 hr before (i-PrO)3B (5.59 mL, 24.3 mmol) was added via syringe. After the addition of (i-PrO)3B, the reaction mixture was warmed to room temperature and allowed to stir for 2 hr before quenching the reaction with equal volume of concentrated NH4Cl(aq) and EtOAc (1:1, 30 mL). The layers were separated and the water phase was further extracted with equal volume of EtOAc before the organic layers were combined and dried over anhydrous Na2SO4 and filtered. The solvent was removed under reduced pressure. The residue was purified by silica gel column using Combiflash to give 6-fluorobenzo[c][1,2]oxaborole-1,5(3H)-diol (2.01 g, 73.93%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm) 4.85 (s, 2H), 6.95 (d, J=5.4 Hz, 1H), 7.36 (d, J=8.1 Hz, 1H), 8.98 (s, 1H), 10.22 (s, 1H).

1. customReaction mixture
2. additionwas then treated
3. additionwas added via syringe
4. temperaturethe reaction mixture was warmed to room temperature
5. custombefore quenching
6. customthe reaction with equal volume of concentrated NH4Cl(aq) and EtOAc (1:1, 30 mL)
7. customThe layers were separated
8. extractionthe water phase was further extracted with equal volume of EtOAc before the organic layers
9. dry with materialdried over anhydrous Na2SO4
10. filtrationfiltered
11. customThe solvent was removed under reduced pressure
12. customThe residue was purified by silica gel column

ORDレコード

ord-a6b9e96d0f824dee815dc3c2927473e0

出典データセット

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09145429B2