Diisopropylamine → 2-Fluoro-5-(2-methoxyethoxy)pyridin-3-ylboronic acid

Temperature

0 °C

To a stirred solution of diisopropylamine (Aldrich, 3.03 mL, 21.2 mmol) in THF (30 mL) in 250 mL round-bottomed flask, nBuLi (Aldrich, 2.5 M in hexanes, 8.12 mL, 20.3 mmol) was added slowly at 0° C. The mixture was stirred at 0° C. for 30 min. The mixture was cooled to −78° C. and 2-fluoro-5-(2-methoxyethoxy)pyridine (1.58 g, 9.23 mmol) in a total of 5 mL THF was added slowly. The orange mixture was stirred at that temperature for 30 min then triisopropyl borate (Aldrich, 4.72 mL, 20.3 mmol) in a total of 5 mL of THF was added slowly. The mixture was stirred at −78° C. for 10 min, then the cold bath was removed and the mixture was stirred at room temperature for 1 h. 1N NaOH (about 70 mL) was added and the layers were separated. The aqueous phase was washed with EtOAc (50 mL) and acidified to about pH 5 with 5 N HCl. The aq phase was extracted with EtOAc (4×50 mL). The combined organic phases were washed with saturated aqueous sodium chloride (50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford 2-fluoro-5-(2-methoxyethoxy)pyridin-3-ylboronic acid (1.76 g, 89% yield) as a pale yellow residue. This material was used without further purification.

1. temperatureThe mixture was cooled to −78° C.
2. stirringThe orange mixture was stirred at that temperature for 30 min
3. stirringThe mixture was stirred at −78° C. for 10 min
4. customthe cold bath was removed
5. stirringthe mixture was stirred at room temperature for 1 h
6. addition1N NaOH (about 70 mL) was added
7. customthe layers were separated
8. washThe aqueous phase was washed with EtOAc (50 mL)
9. extractionThe aq phase was extracted with EtOAc (4×50 mL)
10. washThe combined organic phases were washed with saturated aqueous sodium chloride (50 mL)
11. dry with materialThe organic phase was dried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD record

ord-2606e67014a943f287214b6d0621fb5b

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362241B2