Sodium Hydroxide → 5-(1,3-Dioxolan-2-yl)-2-fluoropyridin-3-ylboronic acid

5-(1,3-Dioxolan-2-yl)-2-fluoropyridine (18.803 g, 111 mmol) was dissolved in THF (300 mL) in a 1 L round-bottom flask, and the flask was cooled in a dry ice/acetone bath under nitrogen. Then, lithium diisopropylamide (2.0 M in heptane/tetrahydrofuran/ethylbenzene; Acros) (89 mL, 178 mmol) was added via syringe over 20 min. After 75 min, triisopropyl borate (40.8 mL, 178 mmol) was added via syringe over 5 minutes, and then the reaction was allowed to slowly warm up to room temperature while being stirred under nitrogen. After 4.5 h, the reaction mixture was treated with 1 N NaOH (300 mL). The layers were separated, and the organic phase was discarded. The aqueous phase was treated with concentrated HCl and 5 N aqueous HCl to lower the pH to about 5. Then, the aqueous phase was extracted with 10:1 DCM/MeOH. The aqueous phase was treated with 5 N HCl during the extractions to maintain the pH at 5-6. Brine was also added to the aqueous phase to aid extraction. The extracts were combined, concentrated, and dried under high vacuum to give 14.56 g of product. m/z (ESI, +ve ion) 214 (M+H)+.

1. temperaturethe flask was cooled in a dry ice/acetone bath under nitrogen
2. waitAfter 4.5 h
3. customThe layers were separated
4. additionThe aqueous phase was treated with concentrated HCl and 5 N aqueous HCl
5. extractionThen, the aqueous phase was extracted with 10:1 DCM/MeOH
6. additionThe aqueous phase was treated with 5 N HCl during the extractions
7. temperatureto maintain the pH at 5-6
8. additionBrine was also added to the aqueous phase
9. extractionextraction
10. concentrationconcentrated
11. customdried under high vacuum

ORD record

ord-b8775724df5b4c7c97ee185f15c880b8

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362241B2