pent-4-ynylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized using 3-phenyl-1-iodopropane and sodium acetylide by conducting the reactions similar to those mentioned in Reference example 29.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)-pyridine (408 mg, 1.50 mmol), bis(triphenylphosphine)palladium(II) chloride (21 mg, 0.029 mmol) and copper (I) iodide (5 mg, 0.029 mmol) in CH2Cl2 (3.0 mL) and NEt3 (1.0 mL) was added 5-phenyl-1-pentyne (324 mg, 2.25 mmol). The mixture was refluxed overnight then cooled to room temperature. Water (2 mL) was added, and solid sodium bicarbonate was added until the aqueous layer was saturated. The mixture was extracted with EtOAc, which was dried over MgSO4, filtered and concentrated. The residue was chromatographed on a silica gel column, eluting with NH4OH/MeOH/EtOAc 0:1:9 and 1:10:90 to afford an oil (411 mg, 80%). MS (CI/NH3) m/z 335 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.65-2.10 (m, 6H), 2.26-2.37 (m, 1H), 2.41-2.47 (m, 2H), 2.48 (s, 3H), 2.61-2.73 (m, 1H), 2.76-2.83 (m, 2H), 3.07-3.16 (m, 1H), 3.89-4.03 (m, 2H), 7.17-7.36 (m, 6H), 8.21-8.26 (m, 2H). The mixture was refluxed overnight The mixture was extracted with EtOAc, which was dried over MgSO4 filtered concentrated The residue was chromatographed on a silica gel column eluting with NH4OH/MeOH/EtOAc 0:1:9 and 1:10:90

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 74 ml (0.118 mol) of n-butyllithium (1.6 molar in hexane) are added dropwise, under a nitrogen atmosphere, to a solution, cooled to -78° C., of 25 ml (0.157 mol) of 5-phenylpentyne in 400 ml of anhydrous diethyl ether. The whole is stirred at -78° C. for 15 minutes and then at 0° C. for 75 minutes. There is then added dropwise to that solution a solution, cooled to -78° C., of 6-methoxy-1-oxa-spiro[2.5]oct-5-en-4-one (11 g; 71.33 mmol) in 80 ml of anhydrous toluene. After 1 hour's stirring at -78° C., the reaction mixture is poured into an aqueous 10% ammonium chloride solution (1000 ml). Conventional treatment of the organic phase yields 22 g (74 mmol) of 4-hydroxy-6-methoxy-4-(5-phenylpenten-1-yl)-1-oxa-spiro[2.5]octene (2 isomers) in the form of an oily residue which is used in the following step without being purified. Hydrogenation of a solution of 22 g (74 mmol) of that mixture of isomers in 610 ml of benzene in the presence of 10 g of Lindlar catalyst for a period of 7 hours results, after filtration and evaporation, in 22 g (73 mmol) of 4-hydroxy-6methoxy-4-(5-phenylpentyl)-1-oxa-spiro[2.5]oct-5-ene in the form of an oily residue which is used in the following step without being purified. at 0° C. for 75 minutes There is then added dropwise to that solution a solution After 1 hour's stirring at -78° C.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 74 ml (0.118 mol) of n-butyllithium (1.6 molar in hexane) are added dropwise, under a nitrogen atmosphere, to a solution, cooled to -78° C., of 25 ml (0.157 mol) of 5-phenylpentyne in 400 ml of anhydrous diethyl ether. The whole is stirred at -78° C. for 15 minutes and then at 0° C. for 75 minutes. There is then added dropwise to that solution a solution, cooled to -78° C., of 6-methoxy-1-oxa-spiro[2.5]oct-5-en-4-one (11 g; 71.33 mmol) in 80 ml of anhydrous toluene. After 1 hour's stirring at -78° C., the reaction mixture is poured into an aqueous 10% ammonium chloride solution (1000 ml). Conventional treatment of the organic phase yields 22 g (74 mmol) of 4-hydroxy-6-methoxy-4-(5-phenylpenten-1-yl)-1-oxa-spiro[2.5]octene (2 isomers) in the form of an oily residue which is used in the following step without being purified. Hydrogenation of a solution of 22 g (74 mmol) of that mixture of isomers in 610 ml of benzene in the presence of 10 g of Lindlar catalyst for a period of 7 hours results, after filtration and evaporation, in 22 g (73 mmol) of 4-hydroxy-6methoxy-4-(5-phenylpentyl)-1-oxa-spiro[2.5]oct-5-ene in the form of an oily residue which is used in the following step without being purified. at 0° C. for 75 minutes There is then added dropwise to that solution a solution After 1 hour's stirring at -78° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Maintain 5-phenylpent-1-yne (20 g) for 12 hours at 70° under nitrogen with water (6.2 cc), trioxan (1.2 g), 30% formalin (13.8 g), diethylamine (10 g), acetic acid (6.9 g), dioxan (62 cc) and cuprous chloride (0.35 g). Make the cooled solution alkaline with sodium hydroxide. Extract with ether and extract the ether extract itself with hydrochloric acid. Make the purified aqueous hydrochloride solution thus obtained alkaline again and extract with ether. Dry, evaporate the ether extracts and distil the residue to obtain 1-diethylamino-6-phenylhex-2-yne (27.1 g), b.p. 104-106°/0.2 mm. Extract with ether extract the ether extract itself with hydrochloric acid extract with ether Dry evaporate the ether extracts distil the residue

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2R)-Acetylamino-2-methyl-4-(5-bromothiophen-2-yl)butyl acetate (1.60 g, 4.59 mmol) obtained in Example 47 (c) was dissolved in dimethylformamide (16 ml), and 5-phenylpent-1-yne (1.99 g, 13.8 mmol), triethylamine (6.40 ml, 45.9 mmol), copper(I) iodide (175 mg, 0.92 mmol), and dichlorobis(triphenylphosphine)palladium (322 mg, 0.46 mmol) were added thereto followed by stirring for 2 hours at 80° C. under a nitrogen atmosphere. The reaction solution was poured into water, extracted with ethyl acetate, and after the ethyl acetate layer was dried over anhydrous magnesium sulfate, the solvent was evaporated in vacuo. The residue was purified by chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=2:1-2:3) to give the title compound (1.41 g, 75% yield). extracted with ethyl acetate after the ethyl acetate layer was dried over anhydrous magnesium sulfate the solvent was evaporated in vacuo The residue was purified by chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=2:1-2:3)