4-bromo-2-chloro-6-fluorophenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-chloro-6-fluoro-phenol (0.500 g, 2.21 mmol) is dissolved in dry THF, the reaction mixture is cooled to −78° C. (dry-ice/acetone bath) and 2.5M n-butylithium (1.06 ml, 2.66 mmol) is slowly added drop wise with stirring for 5 minutes. TMSCl (0.298 ml, 2.33 mmol) is added drop wise maintaining the temperature below −70° C. and the reaction mixture is stirred for 30 minutes. Boric acid triethyl ester is then added (0.385 ml, 2.26 mmol) followed by the second addition of n-butylitlium (1.06 ml, 2.66 mmol) maintaining the temperature below −65° C. The reaction mixture is stirred at −70° C. for 30 minutes then quenched with 5M HCl (5 ml) and allowed to warm to room temperature with stirring for 30 minutes. The reaction mixture is diluted with water and EtOAc and the organic portion is washed with 5M NaOH. The aqueous layer is acidified with 5M HCl and extracted with EtOAc, this organic portion is washed with brine, dried over MgSO4 and concentrated in vacuo to afford the title compound as an off white solid. wise maintaining the temperature below −70° C. the reaction mixture is stirred for 30 minutes followed by the second addition of n-butylitlium (1.06 ml, 2.66 mmol) maintaining the temperature below −65° C The reaction mixture is stirred at −70° C. for 30 minutes then quenched with 5M HCl (5 ml) with stirring for 30 minutes The reaction mixture is diluted with water and EtOAc the organic portion is washed with 5M NaOH extracted with EtOAc this organic portion is washed with brine dried over MgSO4 concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Cyanophenylboronic acid and 4-bromo-2-chloro-6-fluorophenol were processed as described in Example 167A to provide the title compound (48% yield). 1HNMR (300 MHz, MeOD) δ7.40 (m, 1H), 7.52 (m, 1H), 7.78 (s, 4H); MS (CDI) m/z 248 (M+H)+.