2-iodoethylbenzene

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:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5 mL (34.5 mmol) of (2-iodoethyl)benzene in 100 mL of ether at −78° C. was added 42.6 mL (72.5 mmol) of t-butyl lithium. The reaction mixture was warmed to −20° C. for 20 min, then cooled to −78° C. TO this solution, was added a solution of 5.6 g (23.2 mmol) of 1-t-butoxy carbonyl-4-formylpiperidine in 50 mL of ether and the reaction mixture was stirred 15 min at −78° C. To the reaction mixture was added 150 mL of a sat'd solution of NH4Cl and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with sat'd NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated. Removal of the BOC protecting group was achieved as described in Example 233, Step 6 to give the title compound. cooled to −78° C the mixture was extracted with ethyl acetate The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered the filtrate was concentrated Removal of the BOC protecting group

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

実験手順: 100 mg of tetrakis (triphenylphosphine) palladium (0) and 50 mg of copper (I) iodide were added to a mixture of 1.21 g (5.00 mmol) of trans-4-(p-ethynylphenyl)-1-n-propyl-1-silacyclohexane, 1.50 g (6.46 mmol) of p-iodoethylbenzene and 30 ml of triethylamine. The reaction mixture was stirred for 20 hours at room temperature. After a conventional after treatment, purification was conducted by means of silica-gel column chromatography to obtain 1.30 g (yield 75%) of the target product. After a conventional after treatment, purification

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

実験手順: 100 mg of tetrakis (triphenylphosphine) palladium (0) and 50 mg of copper (I) iodide were added to a mixture of 1.21 g (5.00 mmol) of trans-4-(p-ethynylphenyl)-1-n-propyl-1-silacyclohexane, 1.50 g (6.46 mmol) of p-iodoethylbenzene and 30 ml of triethylamine. The reaction mixture was stirred for 20 hours at room temperature. After a conventional after treatment, purification was conducted by means of silica-gel column chromatography to obtain 1.30 g (yield 75%) of the target product. After a conventional after treatment, purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 200 ml of tetrahydrofuran containing 140 mmol lithium diisopropylamide was added 15 g of solid 1-benzoyl-2-piperidinecarbonitrile at -78° C. The mixture was stirred for 30 minutes, after which 100 ml of tetrahydrofuran containing 33.2 g of phenethyl iodide was added dropwise at -78° C. After completion of dropwise addition, the temperature of the reaction mixture was gradually increased to 0° C. Then, water was added and the organic layer was separated. The aqueous layer was further extracted with ethyl acetate. The pooled organic layer was dried over anhydrous magnesium sulfate and filtered and the solvent was then distilled off. The residue was purified by silica gel column chromatography using ethyl acetate-hexane (1:2) as the eluent. The solution containing the desired compound was distilled under reduced pressure and the resulting solid was recrystallized from ethyl acetate-hexane to provide 17.3 g of colorless crystals. After completion of dropwise addition the organic layer was separated The aqueous layer was further extracted with ethyl acetate The pooled organic layer was dried over anhydrous magnesium sulfate filtered the solvent was then distilled off The residue was purified by silica gel column chromatography The solution containing the desired compound was distilled under reduced pressure the resulting solid was recrystallized from ethyl acetate-hexane

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

実験手順: Iodine (12.0 g, 47.4 mmol) was added in one portion to a solution of 2-phenylethanol (5.11 g, 36.5 mmol), triphenylphosphine (11.47 g, 43.8 mmol) and imidazole (3.48 g, 51.04 mmol) in dichloromethane (250 mL) at 0° C. The resulting mixture was allowed to warm slowly to rt and stir overnight, then was transferred to a separatory funnel and washed with water (2×250 mL), saturated aqueous Na2S2O3 (2×100 mL), water (100 mL), and brine (100 mL). The organic phase was dried over MgSO4, filtered and concentrated to a colorless oil that contained a large amount of white solid. The mixture was treated with heptane (2×50 mL) and was filtered. The filtrate was concentrated and the resulting material was again treated with heptane (2×50 mL) and filtered. The filtrate was concentrated to provide 2-phenylethyl iodide as a clear colorless oil (1.74 g, 19%) that contained a trace amount of triphenylphosphine oxide. was transferred to a separatory funnel washed with water (2×250 mL), saturated aqueous Na2S2O3 (2×100 mL), water (100 mL), and brine (100 mL) The organic phase was dried over MgSO4 filtered concentrated to a colorless oil that The mixture was treated with heptane (2×50 mL) was filtered The filtrate was concentrated the resulting material was again treated with heptane (2×50 mL) filtered The filtrate was concentrated

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

実験手順: Following the procedure as described in Example 5, making variations to replace benzyl bromide with (2-iodoethyl)benzene to react with ethyl 4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate, the title compound was obtained in 35% yield: 1H NMR (300 MHz, CDCl3) δ 7.31-7.20 (m, 5H), 4.25 (q, 1=7.2 Hz, 2H), 4.02 (t, J=7.8 Hz, 2H), 3.57 (t, J=7.2 Hz, 2H), 3.42 (t, J=7.8 Hz, 2H), 2.89 (t, J=7.2 Hz, 2H), 2.59 (s, 3H), 1.31 (t, J=7.2 Hz, 3H): MS (ES+) m/z 360.2 (M+1).

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

実験手順: A mixture of 1′-{[1-(4-hydroxyphenyl)cyclopropyl]carbonyl}-3H-spiro[furo[3,4-c]pyridine-1,3′-pyrrolidin]-3-one (15 mg, purity: 80%, 0.034 mmol), (2-iodoethyl)-benzene (12 mg, 0.051 mmol), and tetra-n-butylammonium iodide (1 mg, 0.003 mmol), and Cesium Carbonate (28 mg, 0.086 mmol) in Dimethyl sulfoxide (0.3 ml) was stirred at r.t. overnight. Then the desired product was obtained from the mixture by prep-HPLC (0.24 mg). LCMS: m/z 455.1 (M+H)+; 477.0 (M+Na)+.

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

実験手順: A mixture of 1′-{[1-(4-hydroxyphenyl)cyclopropyl]carbonyl}-3H-spiro[furo[3,4-c]pyridine-1,3′-pyrrolidin]-3-one (15 mg, purity: 80%, 0.034 mmol), (2-iodoethyl)-benzene (12 mg, 0.051 mmol), and tetra-n-butylammonium iodide (1 mg, 0.003 mmol), and Cesium Carbonate (28 mg, 0.086 mmol) in Dimethyl sulfoxide (0.3 ml) was stirred at r.t. overnight. Then the desired product was obtained from the mixture by prep-HPLC (0.24 mg). LCMS: m/z 455.1 (M+H)+; 477.0 (M+Na)+.

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5 mL (34.5 mmol) of (2-iodoethyl)benzene in 100 mL of ether at −78° C. was added 42.6 mL (72.5 mmol) of t-butyl lithium. The reaction mixture was warmed to −20° C. for 20 min, then cooled to −78° C. TO this solution, was added a solution of 5.6 g (23.2 mmol) of 1-t-butoxy carbonyl-4-formylpiperidine in 50 mL of ether and the reaction mixture was stirred 15 min at −78° C. To the reaction mixture was added 150 mL of a sat'd solution of NH4Cl and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with sat'd NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated. Removal of the BOC protecting group was achieved as described in Example 233, Step 6 to give the title compound. cooled to −78° C the mixture was extracted with ethyl acetate The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered the filtrate was concentrated Removal of the BOC protecting group

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5 mL (34.5 mmol) of (2-iodoethyl)benzene in 100 mL of ether at −78° C. was added 42.6 mL (72.5 mmol) of t-butyl lithium. The reaction mixture was warmed to −20° C. for 20 min, then cooled to −78° C. TO this solution, was added a solution of 5.6 g (23.2 mmol) of 1-t-butoxy carbonyl-4-formylpiperidine in 50 mL of ether and the reaction mixture was stirred 15 min at −78° C. To the reaction mixture was added 150 mL of a sat'd solution of NH4Cl and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with sat'd NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated. Removal of the BOC protecting group was achieved as described in Example 233, Step 6 to give the title compound. cooled to −78° C the mixture was extracted with ethyl acetate The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered the filtrate was concentrated Removal of the BOC protecting group