4-Bromo-2-chloro-1-(trifluoromethoxy)benzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-chloro4-trifluoromethoxyaniline (5.1 g) in acetic acid (31 ml) was stirred and treated with sodium nitrite (2.16 g) in concentrated sulphuric acid (14 ml) at below 18° C. After an additional 1 hour at 10° C., the solution was added to a mixture of copper (I) bromide (7.7 g) and hydrobromic acid (24.5 ml) in water at 40-50° C. The reaction was completed by heating at 50° C. for 2 hours, water was added and the mixture filtered. The filtrate was extracted with ether, washed with sodium bicarbonate, dried (magnesium sulphate) and evaporated to give 3-chloro-4-trifluoromethoxy-bromobenzene (6.05 g) as a brown oil, NMR (CDCl3) 7.10(m,1H), 7.35(m,1H), 7.55(d,1H). the mixture filtered The filtrate was extracted with ether washed with sodium bicarbonate dried (magnesium sulphate) evaporated

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

実験手順: A solution of n-butyl lithium (4.4 ml of 2.5M solution in hexanes) in dry diisopropyl ether was treated at −78° C. under an inert atmosphere with 3-chloro4-trifluoromethoxy-bromobenzene (2.96 g) in diisopropyl ether. After 10 minutes, excess carbon dioxide (in the form of pellets) was added and the mixture left to slowly warm to ambient temperature. Ice-water was added and the organic layer run off. The aqueous layer was acidified with dilute hydrochloric acid, extracted (ether), dried (magnesium sulphate) and evaporated to dryness to give 3-chloro-4-trifluoromethoxybenzoic acid (1.51 g) as a white solid, m.p. 110.5-111.5° C. the mixture left extracted (ether) dried (magnesium sulphate) evaporated to dryness

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

実験手順: A solution of n-butyl lithium (4.4 ml of 2.5M solution in hexanes) in dry diisopropyl ether was treated at −78° C. under an inert atmosphere with 3-chloro4-trifluoromethoxy-bromobenzene (2.96 g) in diisopropyl ether. After 10 minutes, excess carbon dioxide (in the form of pellets) was added and the mixture left to slowly warm to ambient temperature. Ice-water was added and the organic layer run off. The aqueous layer was acidified with dilute hydrochloric acid, extracted (ether), dried (magnesium sulphate) and evaporated to dryness to give 3-chloro-4-trifluoromethoxybenzoic acid (1.51 g) as a white solid, m.p. 110.5-111.5° C. the mixture left extracted (ether) dried (magnesium sulphate) evaporated to dryness

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 0° C. solution consisting of 3-chloro-4-trifluoromethoxy-aniline (2.12 g, 10.0 mmol) and HBr (48% aq, 50 mL) was added NaNO2 (2 M aq., 917.7 mg, 13.3 mmol) dropwise at a rate such that the reaction temperature remained below 5° C. After stirring for 1.75 h, urea (330 mg, 5.5 mmol) was added and the mixture stirred for 20 min. A solution consisting of Cu(I)Br (2.96 g, 20.6 mmol) and HBr (48% aq., 13.1 mL) was then added while keeping the reaction temperature in the range of 0-5° C. Upon complete addition, the reaction mixture was heated to 85° C. for 2.5 h. After cooling to rt, the reaction mixture was poured into ice water (150 mL) and extracted with hexanes (100 mL). The aqueous layer was washed with CH2Cl2 (100 mL) and the combined organic phases washed with satd. aq. NaHCO3 (150 mL×2), dried (Na2SO4) and concentrated. The crude material was purified (FCC) to yield the title compound (806 mg, 29%). To a 0° C. remained below 5° C the mixture stirred for 20 min was then added in the range of 0-5° C Upon complete addition After cooling to rt extracted with hexanes (100 mL) The aqueous layer was washed with CH2Cl2 (100 mL) the combined organic phases washed with satd aq. NaHCO3 (150 mL×2), dried (Na2SO4) concentrated The crude material was purified (FCC)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-chloro4-trifluoromethoxyaniline (5.1 g) in acetic acid (31 ml) was stirred and treated with sodium nitrite (2.16 g) in concentrated sulphuric acid (14 ml) at below 18° C. After an additional 1 hour at 10° C., the solution was added to a mixture of copper (I) bromide (7.7 g) and hydrobromic acid (24.5 ml) in water at 40-50° C. The reaction was completed by heating at 50° C. for 2 hours, water was added and the mixture filtered. The filtrate was extracted with ether, washed with sodium bicarbonate, dried (magnesium sulphate) and evaporated to give 3-chloro-4-trifluoromethoxy-bromobenzene (6.05 g) as a brown oil, NMR (CDCl3) 7.10(m,1H), 7.35(m,1H), 7.55(d,1H). the mixture filtered The filtrate was extracted with ether washed with sodium bicarbonate dried (magnesium sulphate) evaporated

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

実験手順: A solution of n-butyl lithium (4.4 ml of 2.5M solution in hexanes) in dry diisopropyl ether was treated at −78° C. under an inert atmosphere with 3-chloro4-trifluoromethoxy-bromobenzene (2.96 g) in diisopropyl ether. After 10 minutes, excess carbon dioxide (in the form of pellets) was added and the mixture left to slowly warm to ambient temperature. Ice-water was added and the organic layer run off. The aqueous layer was acidified with dilute hydrochloric acid, extracted (ether), dried (magnesium sulphate) and evaporated to dryness to give 3-chloro-4-trifluoromethoxybenzoic acid (1.51 g) as a white solid, m.p. 110.5-111.5° C. the mixture left extracted (ether) dried (magnesium sulphate) evaporated to dryness