Hydrochloric Acid → HCID 67440495, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 6-(2-fluoro-3-formyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-2-methoxynicotinonitrile (1.45 g, 3.64 mmol) in methanol (15 mL) was put on an ice water bath. Sodium borohydride was added in portions. The reaction was stirred at 0° C. for five minutes and then stirred at room temperature for 2 hours. The reaction was cooled again to 0° C. on an ice water bath and sodium borohydride (0.034 g, 0.91 mmol) was added. The reaction was stirred at room temperature for 1 hour. The reaction was again cooled to 0° C. and sodium borohydride (0.034 g, 0.91 mmol) was again added. The reaction was stirred at room temperature for one hour. The reaction was neutralized to pH 6 to 7 using 1 M HCl. The solution was then extracted using ethyl acetate and 0.5 M boronic acid solution in water. The organic layer was washed two more times with the 0.5 M boronic acid solution, then washed with brine, dried over anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure. The residue was purified by silica gel column using Combiflash to give 6-(4-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-methoxynicotinonitrile (0.220 g, 20% yield). ES(−) MS m/z=300 (M−H)−; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.67 (s, 3 H), 5.11 (s, 2 H), 6.82 (d, J=8.2 Hz, 1 H), 7.39 (t, J=6.8, J=7.5 Hz, 1 H), 7.60 (d, J=7.8 Hz, 1 H), 8.28 (d, J=8.2 Hz, 1 H), 9.47 (s, 1 H).

Provenance & Evidence