1-(4-bromo-2-chlorophenyl)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:

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 stirred solution of 1-(4-bromo-2-chlorophenyl)-1-ethanone (11.58 g, 50 mmol) in dioxane (12 ml) was added a solution of bromine (8.12 g, 51 mmol) in dioxane (46 ml), and the mixture was stirred for 3 hours. Then the volatile was evaporated in vacuo. The residue was used for next reaction without purification. (15.6 g, 99% yield). Then the volatile was evaporated in vacuo The residue was used for next reaction without purification

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

Procedure: To a stirred solution of methylmagnesium iodide (0.82 M solution in diethylether; 113 ml, 92.4 mmol) was added a solution of 4-bromo-2-chlorobenzonitrile (10 g, 46.2 mmol) in diethylether (92 ml) dropwise, and the mixture was heated at reflux temperature for 16 hours. The mixture was cooled down to room temperature, added concentrated hydrochloric acid (50 ml), and the mixture was stirred for 5 hours. The whole was extracted with diethylether. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography eluting with ethyl acetate-hexane (1:10) to give title compound (7.77 g, 72% yield). the mixture was heated at reflux temperature for 16 hours The whole was extracted with diethylether The organic layer was washed with brine dried over MgSO4 concentrated in vacuo The residue was purified by flash chromatography eluting with ethyl acetate-hexane (1:10)

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:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyllithium (1.6M) in hexanes (0.18 ml) was added to a solution of diisopropylamine (0.212 ml) in THF (2 ml) at 0° C. The mixture was stirred for 5 min and then cooled to −78° C. 3-Methylthiophene-2-carbonitrile (184 mg, CAS Reg. No. 55406-13-8) was added at −78° C. and then stirred for 30 min. A solution of 2-(4-bromo-2-chlorophenyl)ethanone (248 mg, CAS Reg. No. 749932-89-6, prepared in analogy to Example 58, step 2, from 2-chloro-4-bromoacetophenone [CAS Reg. No. 252561-81-2]) in THF (1 ml) was added at −78° C. The mixture was stirred for 20 min, then water (0.2 ml) was added. The mixture was filtered over celite and concentrated to an oil. The residue was purified by flash chromatography (SiO2, 0 to 100% EtOAc/heptane) to give the title compound (100 mg) as a colorless oil. MS (m/e)=370.0 [M+H+]. 55406-13-8) was added at −78° C. stirred for 30 min The mixture was stirred for 20 min The mixture was filtered over celite concentrated to an oil The residue was purified by flash chromatography (SiO2, 0 to 100% EtOAc/heptane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of n-butyllithium (1.6M) in hexanes (0.18 ml) was added to a solution of diisopropylamine (0.212 ml) in THF (2 ml) at 0° C. The mixture was stirred for 5 min and then cooled to −78° C. 3-Methylthiophene-2-carbonitrile (184 mg, CAS Reg. No. 55406-13-8) was added at −78° C. and then stirred for 30 min. A solution of 2-(4-bromo-2-chlorophenyl)ethanone (248 mg, CAS Reg. No. 749932-89-6, prepared in analogy to Example 58, step 2, from 2-chloro-4-bromoacetophenone [CAS Reg. No. 252561-81-2]) in THF (1 ml) was added at −78° C. The mixture was stirred for 20 min, then water (0.2 ml) was added. The mixture was filtered over celite and concentrated to an oil. The residue was purified by flash chromatography (SiO2, 0 to 100% EtOAc/heptane) to give the title compound (100 mg) as a colorless oil. MS (m/e)=370.0 [M+H+]. 55406-13-8) was added at −78° C. stirred for 30 min The mixture was stirred for 20 min The mixture was filtered over celite concentrated to an oil The residue was purified by flash chromatography (SiO2, 0 to 100% EtOAc/heptane)