4-BroMo-1-Chloro-2-ethoxy-benzene

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

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

Procedure: To a solution of 31A (3.8 g, 16 mmol) in THF (20 mL) at −78° C. was added n-BuLi (1.6 M in hexanes, 13.6 mL, 21.8 mmol). The mixture was stirred at −78° C. for 40 min before triisopropyl borate (7.43 mL, 32 mmol) was added. The reaction was left stirring, from −78° C. to rt over 18 h. It was quenched with 1.0 N HCl (50 mL), extracted with EtOAc, washed with brine and dried over Na2SO4. The crude residue was purified by flash column chromatography (CH2Cl2: EtOAc: MeOH=50:50:1) to give 1.85 g (57%) of 31B as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.53 (t, J=7.03 Hz, 3H) 4.23 (d, J=7.03 Hz, 2H) 7.48 (d, J=7.91 Hz, 1H) 7.66 (d, J=6.15 Hz, 2H). was added The reaction was left It was quenched with 1.0 N HCl (50 mL) extracted with EtOAc washed with brine dried over Na2SO4 The crude residue was purified by flash column chromatography (CH2Cl2: EtOAc: MeOH=50:50:1)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-chloro-5-bromophenol (WO98/003464 which is incorporated herein by reference, 3.43 g, 16.5 mmol) and K2CO3 (4.57 g, 33.0 mmol) in DMF (20 mL) was added ethyl iodide (1.78 mL, 22.3 mmol) at rt. The mixture was heated at 55° C. for 3.0 h. After cooling to rt, the reaction was diluted with ether, washed with water and brine, and dried over MgSO4. The crude residue was purified by flash column chromatography to give 3.85 g (99%) of 31A as viscous oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (t, J=7.03 Hz, 3H) 4.08 (d, J=7.03 Hz, 2H) 7.03 (m, 2H) 7.22 (d, J=6.15 Hz, 2H). After cooling to rt washed with water and brine dried over MgSO4 The crude residue was purified by flash column chromatography

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

Procedure: 8.7 g (357.06 mmol) of Mg and a small amount of iodine were dissolved in 200 ml of THF, and 84.6 g (324.6 mmol) of 1-bromo-4-chloro-3-ethoxybenzene dissolved in 500 ml of THF was added dropwise to the resulting solution. After addition, the resulting mixture was refluxed for 3 hours to prepare a Grignard reagent which was then cooled to room temperature. Thereafter, a Grignard reagent containing 50.2 g (357.06 mmol) of benzoyl chloride was added dropwise to the obtained product and stirred for 5 hours. After a reaction, the reaction solution was washed with water, the solvent was removed, and the obtained product was purified by column chromatography to obtain a benzophenone derivative represented by the following formula (42) as 29.6 g (113.6 mmol, yield of 35%) of a white solid. was added dropwise to the resulting solution After addition the resulting mixture was refluxed for 3 hours After a reaction the reaction solution was washed with water the solvent was removed the obtained product was purified by column chromatography