2-bromo-1-(4-bromo-3-fluorophenyl)ethanone

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromo-1-(4-bromo-3-fluorophenyl)-ethanone [CAS 1003879-02-4] (32.3 g, 109 mmol) was dissolved in ethanol (250 ml). The reaction mixture was cooled to 5° C. to give a yellow suspension. Sodiumborohydride (4.13 g, 109 mmol) was added over 5 min. The reaction mixture was stirred at room temperature for 1 hour. Sodium methoxide (2.95 g, 54.6 mmol) was added. The reaction mixture was stirred at 50° C. for 6 h. The reaction mixture was poured into tert.butyl methyl ether and extracted with brine. The organic layer was dried over MgSO4 and concentrated in vacuo to yield a yellow oil (25.1 g, 94%). GC-EI-MS: 216 ([M.+]). to give a yellow suspension The reaction mixture was stirred at 50° C. for 6 h extracted with brine The organic layer was dried over MgSO4 concentrated in vacuo

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromo-1-(4-bromo-3-fluorophenyl)-ethanone [CAS 1003879-02-4] (32.3 g, 109 mmol) was dissolved in ethanol (250 ml). The reaction mixture was cooled to 5° C. to give a yellow suspension. Sodiumborohydride (4.13 g, 109 mmol) was added over 5 min. The reaction mixture was stirred at room temperature for 1 hour. Sodium methoxide (2.95 g, 54.6 mmol) was added. The reaction mixture was stirred at 50° C. for 6 h. The reaction mixture was poured into tert.butyl methyl ether and extracted with brine. The organic layer was dried over MgSO4 and concentrated in vacuo to yield a yellow oil (25.1 g, 94%). GC-EI-MS: 216 ([M.+]). to give a yellow suspension The reaction mixture was stirred at 50° C. for 6 h extracted with brine The organic layer was dried over MgSO4 concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4-bromo-2-fluorobenzoyl chloride (33 g, CAS 151982-51-3) in acetonitrile (150 ml) and THF (150 ml) at 0-5° C. was added dropwise (trimethylsilyl)diazomethane (83.4 ml, 2 M solution in hexane). The reaction mixture was stirred at room temperature for 30 min. TLC analysis showed the reaction was complete. 37% Hydrochloric acid (23.2 ml) was then added dropwise at 0-5° C. and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was then poured into EtOAc and extracted sequentially with aq. Na2CO3 solution, water and saturated brine. The organic layer was then dried over Na2SO4 and concentrated in vacuo to afford a ca 1:1 mixture of 2-bromo-1-(4-bromo-3-fluoro-phenyl)-ethanone and 2-chloro-1-(4-bromo-3-fluoro-phenyl)-ethanone (34.4 g, 98%) as a yellow solid which was used in the next step without further purification. MS (EI): 203 ([{81Br}M-CH2Cl]+, 201 ([{79Br}M-CH2Cl]+). the reaction mixture was stirred at room temperature for 1 hour extracted sequentially with aq. Na2CO3 solution, water and saturated brine The organic layer was then dried over Na2SO4 concentrated in vacuo to afford a ca was used in the next step without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4-bromo-2-fluorobenzoyl chloride (33 g, CAS 151982-51-3) in acetonitrile (150 ml) and THF (150 ml) at 0-5° C. was added dropwise (trimethylsilyl)diazomethane (83.4 ml, 2 M solution in hexane). The reaction mixture was stirred at room temperature for 30 min. TLC analysis showed the reaction was complete. 37% Hydrochloric acid (23.2 ml) was then added dropwise at 0-5° C. and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was then poured into EtOAc and extracted sequentially with aq. Na2CO3 solution, water and saturated brine. The organic layer was then dried over Na2SO4 and concentrated in vacuo to afford a ca 1:1 mixture of 2-bromo-1-(4-bromo-3-fluoro-phenyl)-ethanone and 2-chloro-1-(4-bromo-3-fluoro-phenyl)-ethanone (34.4 g, 98%) as a yellow solid which was used in the next step without further purification. MS (EI): 203 ([{81Br}M-CH2Cl]+, 201 ([{79Br}M-CH2Cl]+). the reaction mixture was stirred at room temperature for 1 hour extracted sequentially with aq. Na2CO3 solution, water and saturated brine The organic layer was then dried over Na2SO4 concentrated in vacuo to afford a ca was used in the next step without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4-bromo-2-fluorobenzoyl chloride (33 g, CAS 151982-51-3) in acetonitrile (150 ml) and THF (150 ml) at 0-5° C. was added dropwise (trimethylsilyl)diazomethane (83.4 ml, 2 M solution in hexane). The reaction mixture was stirred at room temperature for 30 min. TLC analysis showed the reaction was complete. 37% Hydrochloric acid (23.2 ml) was then added dropwise at 0-5° C. and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was then poured into EtOAc and extracted sequentially with aq. Na2CO3 solution, water and saturated brine. The organic layer was then dried over Na2SO4 and concentrated in vacuo to afford a ca 1:1 mixture of 2-bromo-1-(4-bromo-3-fluoro-phenyl)-ethanone and 2-chloro-1-(4-bromo-3-fluoro-phenyl)-ethanone (34.4 g, 98%) as a yellow solid which was used in the next step without further purification. MS (EI): 203 ([{81Br}M-CH2Cl]+, 201 ([{79Br}M-CH2Cl]+). the reaction mixture was stirred at room temperature for 1 hour extracted sequentially with aq. Na2CO3 solution, water and saturated brine The organic layer was then dried over Na2SO4 concentrated in vacuo to afford a ca was used in the next step without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of the mixture of 2-bromo-1-(4-bromo-3-fluoro-phenyl)-ethanone and 2-chloro-1-(4-bromo-3-fluoro-phenyl)-ethanone (6.16 g) in ethanol (100 ml) at 5° C. was added portionwise over 5 min NaBH4 (788 mg). The reaction mixture was then stirred at room temperature for 1 hour to afford a light yellow solution. TLC analysis showed the reaction was complete. Sodium methoxide (562 mg) was then added and the reaction mixture was stirred at room temperature overnight. TLC analysis showed a small amount of starting material remaining and so the reaction mixture was stirred at 40° C. for 1 h. The reaction mixture was then poured into water and extracted twice with EtOAc. The combined organic layers were washed with saturated brine, then dried over Na2SO4 and concentrated in vacuo to afford (RS)-2-(4-bromo-3-fluoro-phenyl)-oxirane (4.69 g) as a yellow oil which was used in the next step without further purification. to afford a light yellow solution the reaction mixture was stirred at room temperature overnight so the reaction mixture was stirred at 40° C. for 1 h extracted twice with EtOAc The combined organic layers were washed with saturated brine dried over Na2SO4 concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 0° C. solution containing 0.55 g of 2-bromo-1-(4-bromo-3-fluorophenyl)ethanone (1.86 mmols) in 9 mL of THF was added 0.32 mL of morpholine (3.72 mmols). After 18 h the reaction mixture was diluted with 100 mL of dichloromethane and washed with water (1×10 mL) and saturated brine solution (1×10 mL). The organic layer was dried over MgSO4, filtered through a frit, and concentrated to a yellow-orange oil which was used without further purification. MS (ES) m/e 302, 303 [M+H]+. washed with water (1×10 mL) and saturated brine solution (1×10 mL) The organic layer was dried over MgSO4 filtered through a frit concentrated to a yellow-orange oil which was used without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 0° C. solution containing 2.4 g of 1-(4-bromo-3-fluorophenyl)ethanone (11.1 mmols) in 56 mL of CHCl3 was added dropwise 0.57 mL of bromine (11.1 mmols). The reaction was stirred at 0° C. for three hours and then allowed to warm to ambient temperature. The reaction mixture was quenched with 10 mL of saturated aqueous Na2S2O3. The layers were separated, and the organics were dried over MgSO4, filtered through a frit, and concentrated to a yellow solid which was used without further purification. to warm to ambient temperature The reaction mixture was quenched with 10 mL of saturated aqueous Na2S2O3 The layers were separated the organics were dried over MgSO4 filtered through a frit concentrated to a yellow solid which was used without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 0° C. solution containing 2.4 g of 1-(4-bromo-3-fluorophenyl)ethanone (11.1 mmols) in 56 mL of CHCl3 was added dropwise 0.57 mL of bromine (11.1 mmols). The reaction was stirred at 0° C. for three hours and then allowed to warm to ambient temperature. The reaction mixture was quenched with 10 mL of saturated aqueous Na2S2O3. The layers were separated, and the organics were dried over MgSO4, filtered through a frit, and concentrated to a yellow solid which was used without further purification. to warm to ambient temperature The reaction mixture was quenched with 10 mL of saturated aqueous Na2S2O3 The layers were separated the organics were dried over MgSO4 filtered through a frit concentrated to a yellow solid which was used without further purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 0° C. solution containing 0.55 g of 2-bromo-1-(4-bromo-3-fluorophenyl)ethanone (1.86 mmols) in 9 mL of THF was added 0.32 mL of morpholine (3.72 mmols). After 18 h the reaction mixture was diluted with 100 mL of dichloromethane and washed with water (1×10 mL) and saturated brine solution (1×10 mL). The organic layer was dried over MgSO4, filtered through a frit, and concentrated to a yellow-orange oil which was used without further purification. MS (ES) m/e 302, 303 [M+H]+. washed with water (1×10 mL) and saturated brine solution (1×10 mL) The organic layer was dried over MgSO4 filtered through a frit concentrated to a yellow-orange oil which was used without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 0° C. solution containing 2.4 g of 1-(4-bromo-3-fluorophenyl)ethanone (11.1 mmols) in 56 mL of CHCl3 was added dropwise 0.57 mL of bromine (11.1 mmols). The reaction was stirred at 0° C. for three hours and then allowed to warm to ambient temperature. The reaction mixture was quenched with 10 mL of saturated aqueous Na2S2O3. The layers were separated, and the organics were dried over MgSO4, filtered through a frit, and concentrated to a yellow solid which was used without further purification. to warm to ambient temperature The reaction mixture was quenched with 10 mL of saturated aqueous Na2S2O3 The layers were separated the organics were dried over MgSO4 filtered through a frit concentrated to a yellow solid which was used without further purification

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Bromo-1-(4-bromo-3-fluorophenyl)-ethanone [CAS 1003879-02-4] (32.3 g, 109 mmol) was dissolved in ethanol (250 ml). The reaction mixture was cooled to 5° C. to give a yellow suspension. Sodiumborohydride (4.13 g, 109 mmol) was added over 5 min. The reaction mixture was stirred at room temperature for 1 hour. Sodium methoxide (2.95 g, 54.6 mmol) was added. The reaction mixture was stirred at 50° C. for 6 h. The reaction mixture was poured into tert.butyl methyl ether and extracted with brine. The organic layer was dried over MgSO4 and concentrated in vacuo to yield a yellow oil (25.1 g, 94%). GC-EI-MS: 216 ([M.+]). to give a yellow suspension The reaction mixture was stirred at 50° C. for 6 h extracted with brine The organic layer was dried over MgSO4 concentrated in vacuo