2-chloro-4-ethyl-1-fluorobenzene

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

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

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

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

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Intermediate 221.1 (100 mg, 0.631 mmol) and PMDTA (0.15 mL) in 5 mL THF at −70° C., was added BuLi (1.4 M in hexanes, 0.473 mL, 0.662 mmol). The mixture was stirred with warming to −40° C. over 30 min, recooled to −70° C., then a solution of Intermediate 175.1 (263 mg, 0.631 mmol) in 2 mL THF was added. The mixture was slowly warmed to −20° C. over 1 h. The reaction was quenched with sat. NH4Cl, then was diluted with EtOAc. The organic phase was washed with H2O (2×) and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient) to afford 312 g of Intermediate 221.2 as a colorless solid. LCMS (50 to 100% B, 4 min gradient, A=95% H2O/5% CH3CN/0.1% TFA, B=5% H2O/95% CH3CN/0.1% TFA) RT=5.45 min, 575.28 (M+H)+. recooled to −70° C. The mixture was slowly warmed to −20° C. over 1 h The reaction was quenched with sat. NH4Cl was diluted with EtOAc The organic phase was washed with H2O (2×) and brine dried (Na2SO4) concentrated The crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient)

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

Procedure: To a solution of 3′-chloro-4′-fluoroacetophenone (5.2 g, 30.1 mmol) in 30 mL TFA, was added triethylsilane (14.4 mL, 90.4 mmol). The mixture was stirred at rt for 15 h, then concentrated. The crude product was purified by flash chromatography (100% hexanes, 2×) to afford 1.35 g of Intermediate 221.1 as a colorless oil. concentrated The crude product was purified by flash chromatography (100% hexanes, 2×)