Trimethyl borate → 2,6-Difluoropyridin-3-ol

Temperatur

-78 °C

To a solution of 2,6-difluoropyridine (6.7 mL, 73.8 mmole) in THF (100 mL, cooled to −78° C.) was added a 2M solution of LDA in heptane/THF/ethylbenene (38 mL, 76 mmol). The mixture was stirred at −78° C. for 1 hour, and trimethyl borate (6.8 mL, 89.7 mmol) was added. The mixture was stirred for 1 hour and allowed to warm to 20° C., then the reaction was quenched with HOAc (10 mL). The solution was made basic with 20% aq NaOH (20 mL), H2O2 (50%, 200 mL) was added, and the mixture stirred for 16 hours. The mixture was neutralized by addition of HCl (2M, aq) and extracted with EtOAc. The combined EtOAc extracts were dried (MgSO4). The solvent was evaporated under vacuum, and the crude product was chromatographed (silica gel; hexane/EtOAc 9:1 to 6:4) to yield 2.7g (28% ) of the title compound. 1H NMR (DMSO-d6, 300 MHz) δ: 6.75 (dd, J=3.0, 5.5 Hz, 1H), 7.48 (m, 1H). MS (DCI/NH3) m/e 149 (M+NH4)+.

1. stirringThe mixture was stirred for 1 hour
2. temperatureto warm to 20° C.
3. customthe reaction was quenched with HOAc (10 mL)
4. additionwas added
5. stirringthe mixture stirred for 16 hours
6. additionThe mixture was neutralized by addition of HCl (2M, aq)
7. extractionextracted with EtOAc
8. dry with materialThe combined EtOAc extracts were dried (MgSO4)
9. customThe solvent was evaporated under vacuum
10. customthe crude product was chromatographed (silica gel; hexane/EtOAc 9:1 to 6:4)

ORD-Eintrag

ord-1a5e46fec90b49d5aba62b4e9f18ad92

Quelldatensatz

uspto-grants-2002_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06403575B1