tert-butyl N-[(1R,3S)-3-(hydroxymethyl)cyclopentyl]carbamate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (1R,3S)-3-t-Butoxycarbonylaminocyclopentanecarboxylic acid (229 mg, 1 mmol) was dissolved in THF (10 mL) and borane-THF (1.5 mL, 1M solution) was added drop-wise at 0° C. and stirred overnight at r.t. The reaction mixture was poured into ice-cold water (10 mL) and extracted with ethyl acetate (2×50 mL). The ethyl acetate extract was washed with brine, dried over sodium sulfate, filtered and evaporated to yield a semi solid (160 mg, 74%). ESMS (+): 216 (M+1)+, 250 (M+Cl)+. extracted with ethyl acetate (2×50 mL) The ethyl acetate extract was washed with brine dried over sodium sulfate filtered evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2.7 g (0.0714 mol) of sodium borohydride are added in portions to a solution of 3.8 g (0.018 mol)of N-BOC-2-azabicyclo[2.2.1 ]heptan3-one in 125 ml of methanol in the course of 20 minutes, while stirring and cooling in an ice-bath. The reaction mixture is further stirred at 0° C. for 1 hour and at room temperature for 1 hour, a solution of 4.08 ml (0.0714 mol) of acetic acid in 8 ml of methanol is then added dropwise and the mixture is evaporated to dryness in vacuo. The crystalline residue is partitioned between methylene chloride and water. After the organic phase has been washed with brine, dried over sodium sulfate and evaporated in vacuo, the title compound is obtained as crystalline residue, m.p. 73°-74° C. cooling in an ice-bath The reaction mixture is further stirred at 0° C. for 1 hour and at room temperature for 1 hour the mixture is evaporated to dryness in vacuo The crystalline residue is partitioned between methylene chloride and water After the organic phase has been washed with brine dried over sodium sulfate evaporated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2.94 ml (0.01755 mol) of diethyl azodicarboxylate (93%) in 10 ml of benzene is added dropwise to a mixture of 3.6 g (0.01672 mol) of cis-3-(N-BOC-amino)-cyclopentanemethanol, 2.73 g (0.01673 mol) of N-hydroxyphthalimide, 4.49 g (0.01672 mol) of triphenylphosphine and 60 ml of benzene at 20°-30° C., while stirring. After the mixture has been stirred at room temperature for 1 hour, the precipitate formed during the reaction is filtered off, the residue on the filter is suspended in benzene and the suspension is filtered again. The latter operation is repeated twice more (residue on the filter: diethyl 1,2-hydrazinedicarboxylate), and the resulting filtrates are combined and these are evaporated in vacuo. Purification of the residue is carried out by means of flash chromatography on silica gel using ethyl acetate/hexane mixtures (1:3 and 1:1). The title compound is thus obtained, m.p. 162°-163° C. After the mixture has been stirred at room temperature for 1 hour the precipitate formed during the reaction is filtered off the suspension is filtered again filter these are evaporated in vacuo Purification of the residue

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2.94 ml (0.01755 mol) of diethyl azodicarboxylate (93%) in 10 ml of benzene is added dropwise to a mixture of 3.6 g (0.01672 mol) of cis-3-(N-BOC-amino)-cyclopentanemethanol, 2.73 g (0.01673 mol) of N-hydroxyphthalimide, 4.49 g (0.01672 mol) of triphenylphosphine and 60 ml of benzene at 20°-30° C., while stirring. After the mixture has been stirred at room temperature for 1 hour, the precipitate formed during the reaction is filtered off, the residue on the filter is suspended in benzene and the suspension is filtered again. The latter operation is repeated twice more (residue on the filter: diethyl 1,2-hydrazinedicarboxylate), and the resulting filtrates are combined and these are evaporated in vacuo. Purification of the residue is carried out by means of flash chromatography on silica gel using ethyl acetate/hexane mixtures (1:3 and 1:1). The title compound is thus obtained, m.p. 162°-163° C. After the mixture has been stirred at room temperature for 1 hour the precipitate formed during the reaction is filtered off the suspension is filtered again filter these are evaporated in vacuo Purification of the residue

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (1R,3S)-3-t-Butoxycarbonylaminocyclopentanecarboxylic acid (229 mg, 1 mmol) was dissolved in THF (10 mL) and borane-THF (1.5 mL, 1M solution) was added drop-wise at 0° C. and stirred overnight at r.t. The reaction mixture was poured into ice-cold water (10 mL) and extracted with ethyl acetate (2×50 mL). The ethyl acetate extract was washed with brine, dried over sodium sulfate, filtered and evaporated to yield a semi solid (160 mg, 74%). ESMS (+): 216 (M+1)+, 250 (M+Cl)+. extracted with ethyl acetate (2×50 mL) The ethyl acetate extract was washed with brine dried over sodium sulfate filtered evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (1R,3S)-3-t-Butoxycarbonylaminocyclopentanecarboxylic acid (229 mg, 1 mmol) was dissolved in THF (10 mL) and borane-THF (1.5 mL, 1M solution) was added drop-wise at 0° C. and stirred overnight at r.t. The reaction mixture was poured into ice-cold water (10 mL) and extracted with ethyl acetate (2×50 mL). The ethyl acetate extract was washed with brine, dried over sodium sulfate, filtered and evaporated to yield a semi solid (160 mg, 74%). ESMS (+): 216 (M+1)+, 250 (M+Cl)+. extracted with ethyl acetate (2×50 mL) The ethyl acetate extract was washed with brine dried over sodium sulfate filtered evaporated

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1.4 g (6.7 mmol) of tert-butyl [(1R,3S)-3-(hydroxymethyl)cyclopentyl]carbamate in 20 mL of anhydrous THF are added portionwise under argon, at room temperature, 0.27 g (6.7 mmol) of sodium hydride at 60% in oil. After stirring for 45 minutes, the medium is cooled to 0° C. and 0.8 mL (6.7 mmol) of benzyl bromide is added. After stirring for 1 hour at room temperature, the medium is hydrolysed with 30 mL of water and extracted with 2×100 mL of EtOAc, dried over Na2SO4, concentrated under reduced pressure and then purified by chromatography on a column of silica gel, eluting with a 99/1 DCM/MeOH mixture. 1.53 g of tert-butyl {(1R,3S)-3-[(benzyloxy)methyl]cyclopentyl}carbamate are obtained in the form of an oil. After stirring for 1 hour at room temperature extracted with 2×100 mL of EtOAc dried over Na2SO4 concentrated under reduced pressure purified by chromatography on a column of silica gel eluting with a 99/1 DCM/MeOH mixture

反应条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2 g (8.7 mmol) of (1S,3R)-3-[(tert-butoxycarbonyl)amino]cyclopentanecarboxylic acid and 1.33 mL (9.6 mmol) of Et3N in 20 mL of anhydrous THF are added dropwise, at −20° C., 1.2 mL (9.2 mmol) of isobutyl chloroformate. The medium is stirred for 45 minutes at −20° C. and the insoluble material formed is then filtered off. A solution of 1 g (26.2 mmol) of sodium borohydride in a THF/H2O mixture (16 mL/4 mL) is added dropwise to the filtrate at −10° C. and stirring is then continued, while allowing the temperature to return to room temperature. 100 mL of 0.1N HCl are then added slowly and the reaction medium is then extracted with 2×200 mL of EtOAc, dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by chromatography on a column of silica gel, eluting with a DCM/MeOH mixture (95/5), 1.4 g of tert-butyl [(1R,3S)-3-(hydroxymethyl)cyclopentyl]carbamate are obtained in the form of an oil. the insoluble material formed is then filtered off stirring to return to room temperature the reaction medium is then extracted with 2×200 mL of EtOAc dried over Na2SO4 filtered concentrated under reduced pressure After purification by chromatography on a column of silica gel eluting with a DCM/MeOH mixture (95/5), 1.4 g of tert-butyl [(1R,3S)-3-(hydroxymethyl)cyclopentyl]carbamate are obtained in the form of an oil

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1.4 g (6.7 mmol) of tert-butyl [(1R,3S)-3-(hydroxymethyl)cyclopentyl]carbamate in 20 mL of anhydrous THF are added portionwise under argon, at room temperature, 0.27 g (6.7 mmol) of sodium hydride at 60% in oil. After stirring for 45 minutes, the medium is cooled to 0° C. and 0.8 mL (6.7 mmol) of benzyl bromide is added. After stirring for 1 hour at room temperature, the medium is hydrolysed with 30 mL of water and extracted with 2×100 mL of EtOAc, dried over Na2SO4, concentrated under reduced pressure and then purified by chromatography on a column of silica gel, eluting with a 99/1 DCM/MeOH mixture. 1.53 g of tert-butyl {(1R,3S)-3-[(benzyloxy)methyl]cyclopentyl}carbamate are obtained in the form of an oil. After stirring for 1 hour at room temperature extracted with 2×100 mL of EtOAc dried over Na2SO4 concentrated under reduced pressure purified by chromatography on a column of silica gel eluting with a 99/1 DCM/MeOH mixture

反应条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2 g (8.7 mmol) of (1S,3R)-3-[(tert-butoxycarbonyl)amino]cyclopentanecarboxylic acid and 1.33 mL (9.6 mmol) of Et3N in 20 mL of anhydrous THF are added dropwise, at −20° C., 1.2 mL (9.2 mmol) of isobutyl chloroformate. The medium is stirred for 45 minutes at −20° C. and the insoluble material formed is then filtered off. A solution of 1 g (26.2 mmol) of sodium borohydride in a THF/H2O mixture (16 mL/4 mL) is added dropwise to the filtrate at −10° C. and stirring is then continued, while allowing the temperature to return to room temperature. 100 mL of 0.1N HCl are then added slowly and the reaction medium is then extracted with 2×200 mL of EtOAc, dried over Na2SO4, filtered and concentrated under reduced pressure. After purification by chromatography on a column of silica gel, eluting with a DCM/MeOH mixture (95/5), 1.4 g of tert-butyl [(1R,3S)-3-(hydroxymethyl)cyclopentyl]carbamate are obtained in the form of an oil. the insoluble material formed is then filtered off stirring to return to room temperature the reaction medium is then extracted with 2×200 mL of EtOAc dried over Na2SO4 filtered concentrated under reduced pressure After purification by chromatography on a column of silica gel eluting with a DCM/MeOH mixture (95/5), 1.4 g of tert-butyl [(1R,3S)-3-(hydroxymethyl)cyclopentyl]carbamate are obtained in the form of an oil

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of tert-butyl (1R,3S)-3-(hydroxymethyl)cyclopentylcarbamate (Step 2, about 4.5 g, 21.12 mmol) in DCM (50 ml), triethyl amine (about 9.5 ml, 68.1 mmol) was added at room temperature and cooled to about 0° C. After ten minutes, 4-methylbenzene-1-sulfonyl chloride (about 6.0 g) was added and stirred the reaction at room temperature for about 6 hours. Completion of the reaction was monitored by TLC. The reaction mixture was neutralized with saturated NaHCO3 and extracted with DCM, the organic layer was dried over Na2SO4 and concentrated under reduced pressure to furnish the title compound (5.5 g) as light yellow liquid. 1H NMR (300 MHz, CDCl3): 1.45 (s, 9H); 246-2.55 (m, 4H); 2.90-2.91 (m, 1H); 3.95-3.98 (m, 2H); 4.59-4.70 (m, 2H); 5.66-5.77 (m, 2H); 7.34-7.37 (d, J=9 Hz, 2H); 7.77-7.80 (d, J=9 Hz, 2H); ES Mass: 369 [M+1] 370 (100%). After ten minutes the reaction at room temperature for about 6 hours extracted with DCM the organic layer was dried over Na2SO4 concentrated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of tert-butyl (1S,4R)-4-(hydroxymethyl)cyclopent-2-enylcarbamate (step 1, about 10.0 g) in ethanol (150 ml) 10% palladium on carbon (about 1.0 g) was added and kept under hydrogen atmosphere. Reaction mass was stirred for about 16 hours. Completion of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was filtered through high-flow bed and washed with ethanol. The filtrate was concentrated under reduced pressure to furnish the title compound (7.5 g) as a light yellow liquid. ES Mass: 215 [M+1] 216 (100%). Reaction mass After completion of the reaction the reaction mixture was filtered through high-flow bed washed with ethanol The filtrate was concentrated under reduced pressure