tert-butyl 4-hydroxy-4-(2-hydroxyethyl)piperidine-1-carboxylate

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

実験手順: 1M solution of borane in THF (15.8 ml, 15.8 mmol) was added slowly to a solution of 2-(1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl)acetic acid (40) (1.02 g, 3.94 mmol) at 0° C. After stirring the mixture at 0° C. for 1 hour and at rt for 16 hours the reaction was quenched by addition of NH4Cl solution and extracted with ethyl acetate. The organic layer was then washed with water and brine, dried over Na2 SO4 and evaporated. The crude product was purified by flash chromatography (silica gel, EtOAc/n-pentane) which furnished the product as colorless oil. at rt for 16 hours the reaction was quenched by addition of NH4Cl solution extracted with ethyl acetate The organic layer was then washed with water and brine dried over Na2 SO4 evaporated The crude product was purified by flash chromatography (silica gel, EtOAc/n-pentane) which

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

実験手順: 1M solution of borane in THF (15.8 ml, 15.8 mmol) was added slowly to a solution of 2-(1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl)acetic acid (40) (1.02 g, 3.94 mmol) at 0° C. After stirring the mixture at 0° C. for 1 hour and at rt for 16 hours the reaction was quenched by addition of NH4Cl solution and extracted with ethyl acetate. The organic layer was then washed with water and brine, dried over Na2 SO4 and evaporated. The crude product was purified by flash chromatography (silica gel, EtOAc/n-pentane) which furnished the product as colorless oil. at rt for 16 hours the reaction was quenched by addition of NH4Cl solution extracted with ethyl acetate The organic layer was then washed with water and brine dried over Na2 SO4 evaporated The crude product was purified by flash chromatography (silica gel, EtOAc/n-pentane) which

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

実験手順: A solution of 21.50 ml (82.50 mmol) of tert-butyldiphenylsilyl chloride in 15 ml of dichloromethane is added dropwise, under an inert atmosphere, to a solution of 18.4 g (75 mmol) of tert-butyl 4-hydroxy-4-(2-hydroxyethyl)-1-piperidinecarboxylate, obtained in step 12.1, and 11.60 ml (82.50 mmol) of triethylamine in 100 ml of dichloromethane, cooled to about 0° C. The mixture is allowed to warm to room temperature and stifling is then continued for 12 hours. Saturated aqueous ammonium chloride solution is added to the reaction medium. The aqueous phase is separated out and extracted twice with dichloromethane, the combined organic phases are washed with saturated aqueous sodium chloride solution and dried over sodium sulfate, and the filtrate is concentrated under reduced pressure. The residue thus obtained is purified by chromatography on silica gel, eluting with a 10/90 and then 20/80 mixture of ethyl acetate and cyclohexane. to warm to room temperature The aqueous phase is separated out extracted twice with dichloromethane the combined organic phases are washed with saturated aqueous sodium chloride solution dried over sodium sulfate the filtrate is concentrated under reduced pressure The residue thus obtained is purified by chromatography on silica gel eluting with a 10/90 20/80 mixture of ethyl acetate and cyclohexane

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

実験手順: A solution of 31.20 g (108.50 mmol) of tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxy-1-piperidinecarboxylate (WO 02/16352) in 150 ml of tetrahydrofuran is added dropwise to a suspension of 4.12 g (108.50 mmol) of lithium aluminium hydride in 150 ml of tetrahydrofuran. The mixture is stirred at room temperature for 2 hours and is then worked up as described in Example 2 (step 2.4).

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

実験手順: A solution of 21.50 ml (82.50 mmol) of tert-butyldiphenylsilyl chloride in 15 ml of dichloromethane is added dropwise, under an inert atmosphere, to a solution of 18.4 g (75 mmol) of tert-butyl 4-hydroxy-4-(2-hydroxyethyl)-1-piperidinecarboxylate, obtained in step 12.1, and 11.60 ml (82.50 mmol) of triethylamine in 100 ml of dichloromethane, cooled to about 0° C. The mixture is allowed to warm to room temperature and stirring is then continued for 12 hours. Saturated aqueous ammonium chloride solution is added to the reaction medium. The aqueous phase is separated out and extracted twice with dichloromethane, the combined organic phases are washed with saturated aqueous sodium chloride solution and dried over sodium sulfate, and the filtrate is concentrated under reduced pressure. The residue thus obtained is purified by chromatography on silica gel, eluting with a 10/90 and then 20/80 mixture of ethyl acetate and cyclohexane. to warm to room temperature The aqueous phase is separated out extracted twice with dichloromethane the combined organic phases are washed with saturated aqueous sodium chloride solution dried over sodium sulfate the filtrate is concentrated under reduced pressure The residue thus obtained is purified by chromatography on silica gel eluting with a 10/90 20/80 mixture of ethyl acetate and cyclohexane

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

実験手順: A solution of 31.20 g (108.50 mmol) of tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxy-1-piperidinecarboxylate (WO 02/16352) in 150 ml of tetrahydrofuran is added dropwise to a suspension of 4.12 g (108.50 mmol) of lithium aluminium hydride in 150 ml of tetrahydrofuran. The mixture is stirred at room temperature for 2 hours and is then worked up as described in Example 2 (step 2.4).

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

実験手順: 1M solution of borane in THF (15.8 ml, 15.8 mmol) was added slowly to a solution of 2-(1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-yl)acetic acid (40) (1.02 g, 3.94 mmol) at 0° C. After stirring the mixture at 0° C. for 1 hour and at rt for 16 hours the reaction was quenched by addition of NH4Cl solution and extracted with ethyl acetate. The organic layer was then washed with water and brine, dried over Na2 SO4 and evaporated. The crude product was purified by flash chromatography (silica gel, EtOAc/n-pentane) which furnished the product as colorless oil. at rt for 16 hours the reaction was quenched by addition of NH4Cl solution extracted with ethyl acetate The organic layer was then washed with water and brine dried over Na2 SO4 evaporated The crude product was purified by flash chromatography (silica gel, EtOAc/n-pentane) which