Hydrochloric Acid → (2,2-Difluoro-1,3-dioxaindan-4-yl)boronic acid

Participants

Reaction Conditions

Reaction Steps

A solution of n-butyllithium (5.57 mL of a 2.5M solution in hexanes, 13.9 mmol) was added to dry tetrahydrofuran (75 mL) at room temperature under a nitrogen atmosphere. The resulting solution was cooled to -15° C. and N,N,N',N'-tetramethylenediamine (2.10 mL, 13.9 mmol) was added dropwise. The reaction was stirred at -15° C. for 0.5 h and then 2,2-difluoro-1,3-benzodioxole was added dropwise while maintaining the reaction temperature below -10° C. After the addition was complete, the reaction was stirred at -15° C. for 1 h before a solution of trimethylborate (1.58 mL, 13.9 mmol) in dry tetrahydrofuran (5 mL) was added dropwise while maintaining the reaction temperature below -10° C. The reaction mixture was stirred at -10° C. for 1 h and then allowed to come to room temperature while stirring overnight. To the reaction mixture was added a 1N solution of hydrochloric acid and then concentrated hydrochloric acid until the solution was strongly acidic. The acidic solution was poured into water. The resulting mixture was saturated with sodium chloride and extracted with diethyl ether three times. The combined organic extracts were dried (MgSO4), filtered, and concentrated under reduced pressure to give a dark-brown oil. The oil was suspended in boiling petroleum ether and the hot solution filtered to remove a small amount of brown solid. The filtrate was then cooled and filtered to obtain a light-gray solid. The filtrate was concentrated under reduced pressure to give a light-brown solid which was combined with the gray solid obtained from recrystallization to afford the title compound of Step F (1.28 g, 50%). 1H NMR (CDCl3): δ4.92 (s,2H), 7.15 (m,2H), 7.5 (d, 1H). 19F NMR (CDCl3): δ-50.33 (s,2F).

Provenance & Evidence