Hydrochloric Acid → (4-(Diisopropylcarbamoyl)-2-ethoxypyridin-3-yl)boronic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of N,N,N′,N′-tetramethylethylenediamine (7.46 ml, 49.4 mmol) in THF (105 ml) at −78° C., sec-butyl lithium (35.3 ml, 49.4 mmol, 1.4 M in cyclohexane) was added. 2-Ethoxy-N,N-diisopropylisonicotinamide (8.25 g, 33.0 mmol) in THF (10 mL) was added slowly over 5 min. After 15 min, trimethyl borate (11.23 ml, 101 mmol) was added and after an additional 30 min, the mixture was allowed to warm to 0° C. To this mixture, aqueous ammonium chloride (saturated, 35 mL) and hydrochloric acid (1 M, 140 mL) were added. The reaction mixture was then allowed to warm to room temperature. After 1 h, the aqueous layer was extracted with CH2Cl2 (140 mL). The organic extract was then washed with aqueous sodium hydroxide (1M, 2×120 mL). The combined aqueous extracts were washed with CH2Cl2 (100 mL), acidified with hydrochloric acid (12 M), and extracted with CH2Cl2 (2×120 mL). The combined organic extracts were washed with brine (100 mL), dried over sodium sulfate, and concentrated under reduced pressure to afford the title compound as a white solid.

Provenance & Evidence