1-iodo-3-(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 according to Example 93, starting with 4-(4-chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3-3(2H)-pyridazinone and substituting 3-iodobenzotrifluoride in place of 4-bromothioanisole (yield: 210 mg, 59.5%). mp 103-105° C. 1H NMR (300 MHz, CDCl3) δ 3.08 (s, 3H), 7.18 (d, J=9 Hz, 2H), 7.28 (d, J=9 Hz, 2H), 7.41 (d, J=9 Hz, 2H), 7.65 (m, 2H), 7.95 (m, 3H), 8.04 (m, 2H). MS (DCI/NH3) m/z 505 (M+H)+, 525 (M+NH4)+. Anal. calc. for C24H16ClF3N2O3S: C, 57.14; H, 5.56. Found: C, 56.61; H, 3.28; N, 5.38.

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

実験手順: Dioxane (100 mL) was purged with nitrogen gas for 10 minutes. Phenanthrolene (1.0 g) and copper (I) iodide (1.0 g) were added to the dioxane, the suspension was allowed to stir under a nitrogen atmosphere for 5 minutes, and then cesium carbonate (18.72 g, 57.45 mmol), dimethyl malonate (5.46 g, 50.6 mmol), and 1-iodo-3-(trifluoromethyl)benzene (12.5 g, 46.0 mmol) were added. The reaction mixture was heated to reflux for 18 hours and then cooled to room temperature. Aqueous 1N HCl was added to the reaction mixture, the layers were separated, and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over magnesium sulfate and filtered. Celite® diatomaceous filter aid (5 g) was added to the filtrate, and the resulting suspension was concentrated under reduced pressure at 50° C. to yield a solid consisting of the crude product adsorbed onto Celite®. This solid was purified by silica gel chromatography eluting with a gradient of 100% hexanes to 25% ethyl acetate in hexanes to yield 7.36 g (58.0%) of the title product. 1H NMR (CDCl3) δ 7.59-7.65 (m, 3H), 7.49 (t, 1H), 4.70 (s, 1H), 3.76 (s, 6H). Dioxane (100 mL) was purged with nitrogen gas for 10 minutes Phenanthrolene (1.0 g) and copper (I) iodide (1.0 g) were added to the dioxane The reaction mixture was heated to reflux for 18 hours the layers were separated the aqueous layer was extracted with ethyl acetate (3×100 mL) The combined organic layers were dried over magnesium sulfate filtered Celite® diatomaceous filter aid (5 g) was added to the filtrate the resulting suspension was concentrated under reduced pressure at 50° C. to yield a solid This solid was purified by silica gel chromatography eluting with a gradient of 100% hexanes to 25% ethyl acetate in hexanes

反応条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-propylmagnesium chloride in THF (1.3 M, 7.5 ml) was cooled to −15° C. and admixed with 1-iodo-3-(trifluoromethyl)benzene (2.80 g, 10.2 mmol). The reaction mixture was stirred at −15° C. for 1 h, warmed to room temperature and admixed dropwise with a solution of 2,2-difluoro-N-methoxy-N-methylpropanamide (1.43 g, 9.35 mmol; prepared according to Synth. Comm. 2008 (38), 1940-1945), and stirred at room temperature overnight. Then the mixture was added to ice-cold dilute hydrochloric acid and extracted with ethyl acetate. The combined organic phases were dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by means of silica gel chromatography with the eluent cyclohexane/ethyl acetate (EA) (0% EA to 30% EA). warmed to room temperature stirred at room temperature overnight Then the mixture was added to ice-cold dilute hydrochloric acid extracted with ethyl acetate The combined organic phases were dried over sodium sulphate concentrated under reduced pressure The residue was purified by means of silica gel chromatography with the eluent cyclohexane/ethyl acetate (EA) (0% EA to 30% EA)

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

実験手順: Methyl 4-[3-(trifluoromethyl)phenyl]-2-oxobutyrate was prepared as an oil from 3-iodobenzotrifluoride and methyl 2-hydroxy-3-butenoate.

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

実験手順: Methyl 4-[3-(trifluoromethyl)phenyl]-2-oxobutyrate was prepared as an oil from 3-iodobenzotrifluoride and methyl 2-hydroxy-3-butenoate.

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 0.02 g (0.10 mmol) of 4-(3-piperidin-1-yl-propyl)-[1,4]diazepan-5-one, 3-iodobenzotrifluoride 0.03 g (0.12 mmol), Pd(OAc)2 0.01 g (0.05 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl 0.03 g (0.05 mmol), cesium carbonate 0.16 g (0.5 mmol) in toluene (1 ml) was heated at 110° C. for 24 h. The reaction was then filtered, concentrated and the residue purified by preparative HPLC affording the title compound 0.1 g (26%) as a gum. MS: 384.2 (MH+). The reaction was then filtered concentrated the residue purified by preparative HPLC