(4-iodophenyl) acetate

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: 4-Pentylphenylacetylene (10.5 g, 61.4 mmol), 4-acetoxyphenyl iodide (16.1 g, 61.4 mmol), a catalytic amount of Pd(PPh3)2Cl2 and a catalytic amount of copper iodide were stirred in diisopropylamine (100 ml) at 70° C. After 5 minutes, a precipitate was seen and the mixture became unstirrable, toluene (100 ml) was added. The mixture was stirred at room temperature for 24 hours and then evaporated to dryness on a rotary evaporator. The residue was redissolved in aqueous potassium hydroxide ethanolic solution and stirred at 70° C. overnight. The mixture was evaporated to dryness, then partitioned between ethyl acetate and water, the organic phase was removed, dried and evaporated. The residue was purified by flash column chromatography using DCM as eluant. A pink coloured solid was left after evaporation of the appropriate fractions. Yield=10.4 g, 64%. 1H-NMR and IR spectroscopy gave the expected signals. evaporated to dryness on a rotary evaporator The residue was redissolved in aqueous potassium hydroxide ethanolic solution stirred at 70° C. overnight The mixture was evaporated to dryness partitioned between ethyl acetate and water the organic phase was removed dried evaporated The residue was purified by flash column chromatography A pink coloured solid was left after evaporation of the appropriate fractions 1H-NMR and IR spectroscopy gave the expected signals

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of acetic acid 4-iodo-phenyl ester (9 gm, 0.0366 mol) in anhydrous DMSO (75 mL) was added copper powder (5.8 g, 0.091 mol), perfluorooctyl iodide (25 g, 0.046 mol) and iodine (130 mg). The reaction mixture was heated to 105° C. for 18 hr, cooled, combined with 100 ml water and 50 ml ether and filtered to remove insoluble copper salts. The organic and aqueous layers in the filtrate were separated, and the aqueous layer extracted twice with ether (2×100 mL). The combined organics were washed with water and brine, dried over MgSO4, and concentrated. To a solution of the crude product in 50 mL methanol was added 1.5 mL 10N HCl. The mixture was refluxed on a steam bath for 1 hr to hydrolyze the acetate completely to the phenol. After cooling to room temperature, the reaction mixture was poured into a separatory funnel containing 100 mL water, and extracted with ether (3×75 mL). The combined organics were washed with water and brine and dried over MgSO4. Recrystallization of the crude concentrate gave 12.5 g of the phenol at 99% purity by HPLC as a waxy solid mp 63-68° C. cooled filtered to remove insoluble copper salts The organic and aqueous layers in the filtrate were separated the aqueous layer extracted twice with ether (2×100 mL) The combined organics were washed with water and brine dried over MgSO4 concentrated To a solution of the crude product in 50 mL methanol was added 1.5 mL 10N HCl The mixture was refluxed on a steam bath for 1 hr After cooling to room temperature the reaction mixture was poured into a separatory funnel containing 100 mL water extracted with ether (3×75 mL) The combined organics were washed with water and brine dried over MgSO4 Recrystallization of the crude concentrate

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

実験手順: Following the basic procedure of Example 11(d), by reacting 1.28 g (5 mmol) of α-ethynyl-5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenemethanol with 1.44 g (5.5 mmol) of 4-iodophenyl acetate, 480 mg (25%) of the expected compound, with a melting point of 129°-130° C., were obtained.

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

実験手順: When 4-iodophenyl acetate and 2-ethynyl-6-methoxybenzofuran were substituted for 4-bromo-N-(6,6-dimethylbicyclo[3.1.1]heptan-2-yl)benzene sulphonamide and but-3-yn-1-ol respectively in Example 18, Step B, the similar process afforded the title compound in 56% yield, as creamy paste. 1H-NMR (CDCl3) 7.56 (d, 2H, J=8.67 Hz); 7.41 (d, 1H, J=8.58 Hz); 7.10 (d, 2H, J=8.7 Hz); 6.97 (d, 1H, J=1.92 Hz); 6.9 (s, 1H); 6.88 (bd, 1H, J=8.61 Hz); 3.85 (s, 3H); 2.3 (s, 3H).

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

実験手順: 4-(2-(1-(tert-Butyldimethylsilyloxy)-7-phenylheptyl)oxazol-5-yl)phenyl acetate. The title compound was prepared from 2-(1-(tert-butyldimethylsilyloxy)-7-phenylheptyl)-5-(tributylstannyl)oxazole (74 mg, 0.112 mmol) and 4-iodophenyl acetate following General Procedure A. Flash chromatography (5-20% EtOAc/hexanes) yielded the title compound as a clear oil (31 mg, 54%): 1H NMR (CDCl3, 600 MHz) δ 7.65 (d, 2H, J=7.8 Hz), 7.27-7.24 (m, 3H), 7.16-7.14 (m, 5H), 4.82 (t, 1H, J=6.0 Hz), 2.58 (t, 2H, J=7.5 Hz), 2.32 (s, 3H), 1.97-1.87 (m, 2H), 1.65-1.60 (m, 2H), 1.45-1.34 (m, 6H), 0.89 (s, 9H), 0.09 (s, 3H), −0.02 (s, 3H); 13C NMR (CDCl3, 150 MHz) δ 170.2, 165.8, 151.4, 151.3, 143.7, 129.2, 129.1, 126.7, 126.4, 126.2, 123.1, 122.4, 69.5, 37.3, 36.8, 32.3, 30.0, 26.6, 26.6, 26.0, 22.1, 19.1, −4.1, −4.2.

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

実験手順: 4-(2-(1-(tert-Butyldimethylsilyloxy)-7-phenylheptyl)oxazol-5-yl)phenyl acetate. The title compound was prepared from 2-(1-(tert-butyldimethylsilyloxy)-7-phenylheptyl)-5-(tributylstannyl)oxazole (74 mg, 0.112 mmol) and 4-iodophenyl acetate following General Procedure A. Flash chromatography (5-20% EtOAc/hexanes) yielded the title compound as a clear oil (31 mg, 54%): 1H NMR (CDCl3, 600 MHz) δ 7.65 (d, 2H, J=7.8 Hz), 7.27-7.24 (m, 3H), 7.16-7.14 (m, 5H), 4.82 (t, 1H, J=6.0 Hz), 2.58 (t, 2H, J=7.5 Hz), 2.32 (s, 3H), 1.97-1.87 (m, 2H), 1.65-1.60 (m, 2H), 1.45-1.34 (m, 6H), 0.89 (s, 9H), 0.09 (s, 3H), −0.02 (s, 3H); 13C NMR (CDCl3, 150 MHz) δ 170.2, 165.8, 151.4, 151.3, 143.7, 129.2, 129.1, 126.7, 126.4, 126.2, 123.1, 122.4, 69.5, 37.3, 36.8, 32.3, 30.0, 26.6, 26.6, 26.0, 22.1, 19.1, −4.1, −4.2.

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: When 4-iodophenyl acetate and 2-ethynyl-6-methoxybenzofuran were substituted for 4-bromo-N-(6,6-dimethylbicyclo [3.1.1]heptan-2-yl)benzene sulphonamide and but-3-yn-1-ol respectively in Example 18, Step B, the similar process afforded the title compound in 56% yield, as creamy paste. 1H-NMR (CDCl3) 7.56 (d, 2H, J=8.67 Hz); 7.41 (d, 1H, J=8.58 Hz); 7.10 (d, 2H, J=8.7 Hz); 6.97 (d, 1H, J=1.92 Hz); 6.9 (s, 1H); 6.88 (bd, 1H, J=8.61 Hz); 3.85 (5, 3H); 2.3 (s, 3H).

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

実験手順: 4-Iodophenyl acetate (50.00 g, 0.191 mol), phenylacetylene (23.40 g, 0.229 mol), and triethylamine (54 mL) are added to a 250-mL round bottom flask fitted with a condenser/nitrogen inlet, a thermometer, and a stopper. PdCl2 (PPh3)2 (0.200 g, 0.286 mmol) and PPh3 (1.50 g, 5.73 mmol) are then added and the mixture heated to reflux. When the reaction mixture reaches 40° C., CuI (0.054 g, 0.286 mmol) is added. After 2 hours, the reaction is allowed to cool. The mixture is diluted with methylene chloride and poured into water (500 mL). The aqueous layer is extracted with methylene chloride (100 mL). The combined organic layers are washed with three 300-mL portions of water, dried (MgSO4), and filtered. The solvent is removed in vacuo to give 49 g of a yellow solid. The material is recrystallized from hexanes to give light yellow crystals, mp 104.5° C. to 105.5° C. fitted with a condenser/nitrogen inlet the mixture heated to reflux reaches 40° C. to cool The aqueous layer is extracted with methylene chloride (100 mL) The combined organic layers are washed with three 300-mL portions of water dried (MgSO4) filtered The solvent is removed in vacuo

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

実験手順: 4-Iodophenyl acetate (50.00 g, 0.191 mol), phenylacetylene (23.40 g, 0.229 mol), and triethylamine (54 mL) are added to a 250-mL round bottom flask fitted with a condenser/nitrogen inlet, a thermometer, and a stopper. PdCl2(PPh3)2 (0.200 g, 0.286 mmol) and PPh3 (1.50 g, 5.73 mmol) are then added and the mixture heated to reflux. When the reaction mixture reaches 40° C., CuI (0.054 g, 0.286 mmol) is added. After 2 hours, the reaction is allowed to cool. The mixture is diluted with methylene chloride and poured into water (500 mL). The aqueous layer is extracted with methylene chloride (100 mL). The combined organic layers are washed with three 300-mL portions of water, dried (MgSO4), and filtered. The solvent is removed in vacuo to give 49 g of a yellow solid. The material is recrystallized from hexanes to give light yellow crystals, mp 104.5° C. to 105.5° C. fitted with a condenser/nitrogen inlet the mixture heated to reflux reaches 40° C. to cool The aqueous layer is extracted with methylene chloride (100 mL) The combined organic layers are washed with three 300-mL portions of water dried (MgSO4) filtered The solvent is removed in vacuo