1-iodo-2-(trifluoromethyl)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: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:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from (R)-2-methyl-4-(3-piperidin-1-yl-propyl)-[1,4]diazepan-5-one and iodobenzotrifluoride in analogy to example 33. MS: 398.3 (MH+).

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

実験手順: Under a nitrogen atmosphere, a solution of 15.0 grams (0.055 mole) of 2-trifluoromethylphenyl iodide, 4.8 grams (0.061 mole) of 4-pentynenitrile, 30.6 mL (0.22 mole) of triethylamine, 0.4 gram (0.0006 mole) of bis(triphenylphosphine)palladium(II) chloride, and 0.1 gram (0.0006 mole) of copper(II) iodide in 50 mL of acetonitrile was stirred at ambient temperature for 5 hours. After this time, gas chromatographic analysis (GC) of the reaction mixture indicated that the reaction was about 60% complete. The reaction mixture was warmed to 40°-45° C., where it was stirred for 16 hours. After this time the reaction mixture was poured into 300 mL of water, and the mixture was extracted with two 100 mL portions of diethyl ether. The combined extracts were washed with aqueous dilute hydrochloric acid and then were dried with magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel. Elution was accomplished using 1:1-methylene chloride and petroleum ether. The product-containing fractions were combined and concentrated under reduced pressure, yielding 11.4 grams of 5-(2-trifluoromethylphenyl)-4-pentynenitrile. The NMR spectrum was consistent with the proposed structure. The reaction mixture was warmed to 40°-45° C. the mixture was extracted with two 100 mL portions of diethyl ether The combined extracts were washed with aqueous dilute hydrochloric acid were dried with magnesium sulfate The mixture was filtered concentrated under reduced pressure to a residual oil Elution concentrated under reduced pressure

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

実験手順: Under a nitrogen atmosphere, a solution of 15.0 grams (0.055 mole) of 2-trifluoromethylphenyl iodide, 4.8 grams (0.061 mole) of 4-pentynenitrile, 30.6 mL (0.22 mole) of triethylamine, 0.4 gram (0.0006 mole) of bis(triphenylphosphine)palladium(II) chloride, and 0.1 gram (0.0006 mole) of copper(II) iodide in 50 mL of acetonitrile was stirred at ambient temperature for 5 hours. After this time, gas chromatographic analysis (GC) of the reaction mixture indicated that the reaction was about 60% complete. The reaction mixture was warmed to 40°-45° C., where it was stirred for 16 hours. After this time the reaction mixture was poured into 300 mL of water, and the mixture was extracted with two 100 mL portions of diethyl ether. The combined extracts were washed with aqueous dilute hydrochloric acid and then were dried with magnesium sulfate. The mixture was filtered and concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel. Elution was accomplished using 1:1-methylene chloride and petroleum ether. The product-containing fractions were combined and concentrated under reduced pressure, yielding 11.4 grams of 5-(2-trifluoromethylphenyl)-4-pentynenitrile. The NMR spectrum was consistent with the proposed structure. The reaction mixture was warmed to 40°-45° C. the mixture was extracted with two 100 mL portions of diethyl ether The combined extracts were washed with aqueous dilute hydrochloric acid were dried with magnesium sulfate The mixture was filtered concentrated under reduced pressure to a residual oil Elution concentrated under reduced pressure

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

実験手順: To a 2-L three-necked, round-bottom flask fitted with a mechanical stirrer and a condenser was added 507.5 g of 2-iodotrifluoromethylbenzene (1.86 mol), 282.0 g of copper powder and 400 ml of DMF. The reaction mixture was stirred and heated at reflux for 24 hours and filtered. The filtrate was distilled under reduced pressure to yield 211.8 g (78%) of a light yellow oil. To a 2-L three-necked, round-bottom flask fitted with a mechanical stirrer and a condenser heated at reflux for 24 hours filtered The filtrate was distilled under reduced pressure

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

実験手順: General Procedure HH: To a solution of 1-iodo-2-(trifluoromethyl)benzene (1.5 g, 5.5 mmol) in THF (10.0 mL) was added 2.5 M of n-BuLi in hexane (2.2 mL) at −78° C. and stirred for 10 min. Propylene oxide (370 mg, 6.4 mmol) was added to the reaction mixture at −78° C. and slowly warmed to rt. The reaction mixture was stirred for an additional 30 min. The reaction mixture was quenched with sat. aq. NH4Cl and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure to give a yellow oil. The material was purified by silica gel chromatography using Hexane/EtOAc (80:20) as eluent to yield the desired product as a colorless oil. 1H NMR (CDCl3, 400 MHz): δ=1.30 (d, J=6.1 Hz, 3H), 1.46 (d, J=4.3 Hz, 1H), 2.82-3.06 (m, 2H), 4.03-4.12 (m, 1H), 7.32-7.38 (m, 1H), 7.41-7.45 (m, 1H), 7.48-7.53 (m, 1H), 7.67 (d, J=8.1 Hz, 1H). The reaction mixture was stirred for an additional 30 min The reaction mixture was quenched with sat. aq. NH4Cl extracted with EtOAc The organic layer was washed with brine dried over anhydrous Na2SO4 the solvent was removed under reduced pressure to give a yellow oil The material was purified by silica gel chromatography

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

実験手順: In analogy to the procedure described in example 5B], (2-methyl-4-prop-2-ynylsulfanyl-phenoxy)-acetic acid tert-butyl ester (example 5A]) and 1-iodo-2-trifluoromethyl-benzene gave the title compound as a light yellow oil.