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

Participants

Reaction Steps

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 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 5N 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)+.

Provenance & Evidence