2-[4-(bromomethyl)phenyl]ethanol

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

実験手順: 3.85 g (18.81 mmol) of 4-bromomethylphenylacetic acid are dissolved in 150 ml of THF, and 20 ml of a 1M solution of BH3 in THF is added slowly with stirring, at 0° C. The reaction mixture is then slowly warmed to room temperature and stirred overnight at room temperature. 2M hydrochloric acid is added, and the reaction mixture is extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and concentrated. 3.64 g (16.92 mmol) of the 2-[4-(bromomethyl)phenyl]ethanol thus obtained are, without further purification, dissolved in 36 ml of DMSO, and 1.65 g (25.38 mmol) of potassium cyanide are added. The reaction mixture is stirred at room temperature for 1 h and then poured into diethyl ether/sat. aqueous sodium bicarbonate solution. The organic phase is washed three times with water, dried over magnesium sulfate, filtered and concentrated. This gives 2.5 g of product. The reaction mixture is then slowly warmed to room temperature stirred overnight at room temperature the reaction mixture is extracted with ethyl acetate The organic phase is dried over magnesium sulfate filtered concentrated

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

実験手順: To a solution of (2-methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 4, step h) (0.791 g) and triethylamine (0.697 mL) in acetonitrile (10 mL) was added 2-(4-(bromomethyl)phenyl)ethanol (example 16, step a) and the resulting mixture stirred overnight. The solvent was evaporated in vacuo. The residue was partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL). The aqueous phase was separated and extracted with ethyl acetate (2×25 mL). The combined organic solutions were washed with brine (25 mL), dried over sodium sulphate, filtered and evaporated in vacuo to give the subtitled compound as a yellow oil. Yield 0.76 g. The solvent was evaporated in vacuo The residue was partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL) The aqueous phase was separated extracted with ethyl acetate (2×25 mL) The combined organic solutions were washed with brine (25 mL) dried over sodium sulphate filtered evaporated in vacuo

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

実験手順: To a solution of (2-methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 4, step h) (0.791 g) and triethylamine (0.697 mL) in acetonitrile (10 mL) was added 2-(4-(bromomethyl)phenyl)ethanol (example 16, step a) and the resulting mixture stirred overnight. The solvent was evaporated in vacuo. The residue was partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL). The aqueous phase was separated and extracted with ethyl acetate (2×25 mL). The combined organic solutions were washed with brine (25 mL), dried over sodium sulphate, filtered and evaporated in vacuo to give the subtitled compound as a yellow oil. Yield 0.76 g. The solvent was evaporated in vacuo The residue was partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL) The aqueous phase was separated extracted with ethyl acetate (2×25 mL) The combined organic solutions were washed with brine (25 mL) dried over sodium sulphate filtered evaporated in vacuo

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

実験手順: Borane dimethylsulphide complex (2M in THF, 4.37 mL) was added dropwise to a solution of 2-(4-(bromomethyl)phenyl)acetic acid (1.0 g) in THF (20 mL) at 20° C. and the mixture stirred for 1 hour. Methanol was added dropwise until bubbling ceased and the solvent evaporated in vacuo. Purification was by silica gel chromatography eluting with 30% ethyl acetate in isohexane. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a white crystalline solid. Yield 0.86 g. until bubbling the solvent evaporated in vacuo Purification eluting with 30% ethyl acetate in isohexane The fractions containing product evaporated in vacuo

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

実験手順: A mixture of 16.9 g (78.5 mmoles) of 4-(bromomethyl)benzeneethanol (prepared according to Plaue S. and Heissler D. Tetrahedron Lett. (1987) 28, 1401-4), 10.6 g (125 mmoles) of 3,4-dihydro-2H-pyrane and 0.16 g of para-toluenesulfonic acid in 160 ml dry ethyl ether, is stirred 16 hours at room temperature. The reaction mixture is thereafter washed with a solution saturated with sodium bicarbonate, then water, dried over Na2SO4 and concentrated, to give 21.5 g (yield=91.5%) of a yellow oil used without other purification. The reaction mixture is thereafter washed with a solution saturated with sodium bicarbonate water, dried over Na2SO4 concentrated

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

実験手順: A mixture of 16.9 g (78.5 mmoles) of 4-(bromomethyl)benzeneethanol (prepared according to Plaue S. and Heissler D. Tetrahedron Lett. (1987) 28, 1401-4), 10.6 g (125 mmoles) of 3,4-dihydro-2H-pyrane and 0.16 g of para-toluenesulfonic acid in 160 ml dry ethyl ether, is stirred 16 hours at room temperature. The reaction mixture is thereafter washed with a solution saturated with sodium bicarbonate, then water, dried over Na2SO4 and concentrated, to give 21.5 g (yield=91.5%) of a yellow oil used without other purification. The reaction mixture is thereafter washed with a solution saturated with sodium bicarbonate water, dried over Na2SO4 concentrated

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

実験手順: To a stirred solution of 3-[3-Methyl-8-(trifluoromethyl)quinolin-4-yl]phenol (0.086 g, 0.28 mmol) and 2-(4-bromomethlyphenyl)ethanol (0.061 g, 0.28 mmol) in CH2Cl2 (5 mL) is added Cs2CO3 (0.365 g, 1.12 mmol). After 1.5 h, additional alkylating agent (0.015 g) is added and the reaction is stirred overnight. The reaction is neutralized with 2N aq HCl, extracted with ethyl acetate and dried (MgSO4). Chromatography eluting with 5:95 ethyl acetate:hexane afforded the title compound (0.092 g, 75%). additional alkylating agent (0.015 g) is added extracted with ethyl acetate dried (MgSO4) Chromatography eluting with 5:95 ethyl acetate

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

実験手順: To a solution of (2-methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 4, step h) (0.791 g) and triethylamine (0.697 mL) in acetonitrile (10 mL) was added 2-(4-(bromomethyl)phenyl)ethanol (example 16, step a) and the resulting mixture stirred overnight. The solvent was evaporated in vacuo. The residue was partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL). The aqueous phase was separated and extracted with ethyl acetate (2×25 mL). The combined organic solutions were washed with brine (25 mL), dried over sodium sulphate, filtered and evaporated in vacuo to give the subtitled compound as a yellow oil. Yield 0.76 g. The solvent was evaporated in vacuo The residue was partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL) The aqueous phase was separated extracted with ethyl acetate (2×25 mL) The combined organic solutions were washed with brine (25 mL) dried over sodium sulphate filtered evaporated in vacuo

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

実験手順: Borane dimethylsulphide complex (2M in THF, 4.37 mL) was added dropwise to a solution of 2-(4-(bromomethyl)phenyl)acetic acid (1.0 g) in THF (20 mL) at 20° C. and the mixture stirred for 1 hour. Methanol was added dropwise until bubbling ceased and the solvent evaporated in vacuo. Purification was by silica gel chromatography eluting with 30% ethyl acetate in isohexane. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a white crystalline solid. Yield 0.86 g. until bubbling the solvent evaporated in vacuo Purification eluting with 30% ethyl acetate in isohexane The fractions containing product evaporated in vacuo

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

実験手順: 3.85 g (18.81 mmol) of 4-bromomethylphenylacetic acid are dissolved in 150 ml of THF, and 20 ml of a 1M solution of BH3 in THF is added slowly with stirring, at 0° C. The reaction mixture is then slowly warmed to room temperature and stirred overnight at room temperature. 2M hydrochloric acid is added, and the reaction mixture is extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and concentrated. 3.64 g (16.92 mmol) of the 2-[4-(bromomethyl)phenyl]ethanol thus obtained are, without further purification, dissolved in 36 ml of DMSO, and 1.65 g (25.38 mmol) of potassium cyanide are added. The reaction mixture is stirred at room temperature for 1 h and then poured into diethyl ether/sat. aqueous sodium bicarbonate solution. The organic phase is washed three times with water, dried over magnesium sulfate, filtered and concentrated. This gives 2.5 g of product. The reaction mixture is then slowly warmed to room temperature stirred overnight at room temperature the reaction mixture is extracted with ethyl acetate The organic phase is dried over magnesium sulfate filtered concentrated

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

実験手順: To a solution of (2-methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 4, step h) (0.791 g) and triethylamine (0.697 mL) in acetonitrile (10 mL) was added 2-(4-(bromomethyl)phenyl)ethanol (example 16, step a) and the resulting mixture stirred overnight. The solvent was evaporated in vacuo. The residue was partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL). The aqueous phase was separated and extracted with ethyl acetate (2×25 mL). The combined organic solutions were washed with brine (25 mL), dried over sodium sulphate, filtered and evaporated in vacuo to give the subtitled compound as a yellow oil. Yield 0.76 g. The solvent was evaporated in vacuo The residue was partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL) The aqueous phase was separated extracted with ethyl acetate (2×25 mL) The combined organic solutions were washed with brine (25 mL) dried over sodium sulphate filtered evaporated in vacuo

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

実験手順: Borane dimethylsulphide complex (2M in THF, 4.37 mL) was added dropwise to a solution of 2-(4-(bromomethyl)phenyl)acetic acid (1.0 g) in THF (20 mL) at 20° C. and the mixture stirred for 1 hour. Methanol was added dropwise until bubbling ceased and the solvent evaporated in vacuo. Purification was by silica gel chromatography eluting with 30% ethyl acetate in isohexane. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a white crystalline solid. Yield 0.86 g. until bubbling the solvent evaporated in vacuo Purification eluting with 30% ethyl acetate in isohexane The fractions containing product evaporated in vacuo