1-(4-chloro-3-fluorophenyl)ethanone

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: The title compound was prepared from 4-acetyl-1-chloro-2-fluorobenzene according to the procedure for preparing 4-(trifluoromethoxy)phenacyl bromide described in Example 189.

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

Procedure: To a solution of 1-bromo-4-chloro-3-fluorobenzene (2.09 g, 10 mmol) in dry diethyl ether (12.0 ml) was added a solution of n-BuLi (1.55M in hexane, 6.77ml, 10.5 mmol) at −78° C. under nitrogen atmosphere. The mixture was allowed to warm to −20_C stirred for 45 min. A solution of N,N-dimethylacetamide (1.04 ml, 11.2 mmol) in diethyl ether (1.5 ml) was added and the mixture stirred for an additional 1 h. The mixture was then allowed to warm to room temperature. After stirring for 3 h, the reaction mixture was poured into saturated aqueous ammonium chloride (20 ml) and extracted with diethyl ether (30 ml×3). The combined organic layers were washed with 2N aqueous HCl (20 ml), saturated aqueous sodium bicarbonate (20 ml), brine (20 ml), and dried (MgSO4). Removal of solvent gave the title compound as a yellow oil (quant.). to warm the mixture stirred for an additional 1 h After stirring for 3 h extracted with diethyl ether (30 ml×3) The combined organic layers were washed with 2N aqueous HCl (20 ml), saturated aqueous sodium bicarbonate (20 ml), brine (20 ml) dried (MgSO4) Removal of solvent

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by following general procedure 3. DMSO was added to NaH (1 equiv.) and heated to 65° C. for 1 h. THF was added at the same temperature and heated for another 10 min. After 10 min., the reaction mixture was cooled to 0° C. Trimethylsulfonium iodide (1 equiv.) was added and stirred for 10 min. after which the solution of 1-(4-chloro-3-fluorophenyl)ethanone (1 equiv.) in THF was added dropwise. After complete addition, the reaction mixture was stirred at RT for 2 h. The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4×50 mL), dried over Na2SO4 and concentrated at 25° C. to obtain the product. heated for another 10 min the reaction mixture was cooled to 0° C was added dropwise After complete addition extracted in diethyl ether (4×50 mL) dried over Na2SO4 concentrated at 25° C. to obtain the product

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

Procedure: The title compound was prepared from 4-acetyl-1-chloro-2-fluorobenzene according to the procedure for preparing 4-(trifluoromethoxy)phenacyl bromide described in Example 189.

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

Procedure: To a solution of 1-bromo-4-chloro-3-fluorobenzene (2.09 g, 10 mmol) in dry diethyl ether (12.0 ml) was added a solution of n-BuLi (1.55M in hexane, 6.77ml, 10.5 mmol) at −78° C. under nitrogen atmosphere. The mixture was allowed to warm to −20_C stirred for 45 min. A solution of N,N-dimethylacetamide (1.04 ml, 11.2 mmol) in diethyl ether (1.5 ml) was added and the mixture stirred for an additional 1 h. The mixture was then allowed to warm to room temperature. After stirring for 3 h, the reaction mixture was poured into saturated aqueous ammonium chloride (20 ml) and extracted with diethyl ether (30 ml×3). The combined organic layers were washed with 2N aqueous HCl (20 ml), saturated aqueous sodium bicarbonate (20 ml), brine (20 ml), and dried (MgSO4). Removal of solvent gave the title compound as a yellow oil (quant.). to warm the mixture stirred for an additional 1 h After stirring for 3 h extracted with diethyl ether (30 ml×3) The combined organic layers were washed with 2N aqueous HCl (20 ml), saturated aqueous sodium bicarbonate (20 ml), brine (20 ml) dried (MgSO4) Removal of solvent

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

Procedure: To a solution of 1-bromo-4-chloro-3-fluorobenzene (2.09 g, 10 mmol) in dry diethyl ether (12.0 ml) was added a solution of n-BuLi (1.55M in hexane, 6.77ml, 10.5 mmol) at −78° C. under nitrogen atmosphere. The mixture was allowed to warm to −20_C stirred for 45 min. A solution of N,N-dimethylacetamide (1.04 ml, 11.2 mmol) in diethyl ether (1.5 ml) was added and the mixture stirred for an additional 1 h. The mixture was then allowed to warm to room temperature. After stirring for 3 h, the reaction mixture was poured into saturated aqueous ammonium chloride (20 ml) and extracted with diethyl ether (30 ml×3). The combined organic layers were washed with 2N aqueous HCl (20 ml), saturated aqueous sodium bicarbonate (20 ml), brine (20 ml), and dried (MgSO4). Removal of solvent gave the title compound as a yellow oil (quant.). to warm the mixture stirred for an additional 1 h After stirring for 3 h extracted with diethyl ether (30 ml×3) The combined organic layers were washed with 2N aqueous HCl (20 ml), saturated aqueous sodium bicarbonate (20 ml), brine (20 ml) dried (MgSO4) Removal of solvent

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: To a solution of the above alcohol (1 eq) in CH2Cl2 (0.3M) at rt was added Dess-Martin periodinane (1.5 eq). The reaction mixture was stirred for 45 minutes at rt and H2O (10 eq) was added. The mixture was stirred for 30 minutes and filtered through silica gel pad eluted with 30% EtOAc/hexane and concentrated. The residue was purified by flash chromatography on silica gel eluted with 20% EtOAc/hexane to give the title compound. The mixture was stirred for 30 minutes filtered through silica gel pad eluted with 30% EtOAc/hexane concentrated The residue was purified by flash chromatography on silica gel eluted with 20% EtOAc/hexane

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by following general procedure 3. DMSO was added to NaH (1 equiv.) and heated to 65° C. for 1 h. THF was added at the same temperature and heated for another 10 min. After 10 min., the reaction mixture was cooled to 0° C. Trimethylsulfonium iodide (1 equiv.) was added and stirred for 10 min. after which the solution of 1-(4-chloro-3-fluorophenyl)ethanone (1 equiv.) in THF was added dropwise. After complete addition, the reaction mixture was stirred at RT for 2 h. The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4×50 mL), dried over Na2SO4 and concentrated at 25° C. to obtain the product. heated for another 10 min the reaction mixture was cooled to 0° C was added dropwise After complete addition extracted in diethyl ether (4×50 mL) dried over Na2SO4 concentrated at 25° C. to obtain the product