tert-butyl N-cyclopropylcarbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:

実験手順: 1f (200 mg, 1.3 mmol) and HBpin (0.28 mL, 1.9 mmol) were used. Purification was performed by MPLC (hexane/ethyl acetate = 10:1 to 3:1) to afford a mixture of 1f and 2f (NMR yield 2%). The mixture was purified again by MPLC (hexane/ethyl acetate = 6:1 to 3:2) to afford 2f as a white solid.

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

実験手順: 8.58 g of N-BOC-cyclopropylamine and 15 g of O-benzyl-3-bromo-1-propanol in 90 ml of DMF are treated at 0°-5° with 2.5 g of sodium hydride (55% in oil). The mixture is stirred at 0°-5° for 1 hour and at room temperature for 3 hours and then treated at 0°-5° with aqueous ammonium chloride solution. The mixture is partitioned in ether/water and the ether phases are washed with water, then dried and concentrated. After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane. Sifter concentration, the residue is crystallized in ether. The crystals are filtered and washed with ether. There are obtained 9.0 g of (3-benzyloxy-propyl)-cyclopropyl-amine hydrochloride, MS (EI): 206 (M+H). The mixture is partitioned in ether/water the ether phases are washed with water dried concentrated After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane Sifter concentration the residue is crystallized in ether The crystals are filtered washed with ether

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

実験手順: 8.58 g of N-BOC-cyclopropylamine and 15 g of O-benzyl-3-bromo-1-propanol in 90 ml of DMF are treated at 0°-5° with 2.5 g of sodium hydride (55% in oil). The mixture is stirred at 0°-5° for 1 hour and at room temperature for 3 hours and then treated at 0°-5° with aqueous ammonium chloride solution. The mixture is partitioned in ether/water and the ether phases are washed with water, then dried and concentrated. After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane. Sifter concentration, the residue is crystallized in ether. The crystals are filtered and washed with ether. There are obtained 9.0 g of (3-benzyloxy-propyl)-cyclopropyl-amine hydrochloride, MS (EI): 206 (M+H). The mixture is partitioned in ether/water the ether phases are washed with water dried concentrated After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane Sifter concentration the residue is crystallized in ether The crystals are filtered washed with ether

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Nitrosonium tetrafluoroborate (9.32 g, 79.8 mmol) was added carefully in several portions to a cooled (−30° C.) solution of N-(tert-butoxycarbonyl)cyclopropylamine (9.57 g, 60.9 mmol) and anhydrous pyridine (11.7 mL) in dry acetonitrile (150 mL). The solution was stirred at −30° C. for 30 minutes, and then at 0° C. for 2 hours. Ice water and EtOAc were added and the organic phase was separated and washed quickly with 1N HCl to remove pyridine. The organic phase was washed with 1N NaHCO3 and brine, dried (MgSO4), filtered, and evaporated under high vacuum with a water bath temperature below 40° C. to give N-nitroso-N-(tert-butoxycarbonyl)amino-cyclopropane (12.1 g, quantitative) as an oil. at 0° C. for 2 hours the organic phase was separated washed quickly with 1N HCl to remove pyridine The organic phase was washed with 1N NaHCO3 and brine dried (MgSO4) filtered evaporated under high vacuum with a water bath temperature below 40° C.

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Nitrosonium tetrafluoroborate (9.32 g, 79.8 mmol) was added carefully in several portions to a cooled (−30° C.) solution of N-(tert-butoxycarbonyl)cyclopropylamine (9.57 g, 60.9 mmol) and anhydrous pyridine (11.7 mL) in dry acetonitrile (150 mL). The solution was stirred at −30° C. for 30 minutes, and then at 0° C. for 2 hours. Ice water and EtOAc were added and the organic phase was separated and washed quickly with 1N HCl to remove pyridine. The organic phase was washed with 1N NaHCO3 and brine, dried (MgSO4), filtered, and evaporated under high vacuum with a water bath temperature below 40° C. to give N-nitroso-N-(tert-butoxycarbonyl)amino-cyclopropane (12.1 g, quantitative) as an oil. at 0° C. for 2 hours the organic phase was separated washed quickly with 1N HCl to remove pyridine The organic phase was washed with 1N NaHCO3 and brine dried (MgSO4) filtered evaporated under high vacuum with a water bath temperature below 40° C.

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

実験手順: 8.58 g of N-BOC-cyclopropylamine and 15 g of O-benzyl-3-bromo-1-propanol in 90 ml of DMF are treated at 0°-5°with 2.5 g of sodium hydride (55% in oil). The mixture is stirred at 0°-5° for 1 hour and at room temperature for 3 hours and then treated at 0°-5° with aqueous ammonium chloride solution. The mixture is partitioned in ether/water and the ether phases are washed with water, then dried and concentrated. After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane. After concentration, the residue is crystallized in ether. The crystals are filtered and washed with ether. There are obtained 9.0 g of (3-benzyloxy-propyl)-cyclopropyl-amine hydrochloride, MS (EI): 206 (M+H). The mixture is partitioned in ether/water the ether phases are washed with water dried concentrated After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane After concentration the residue is crystallized in ether The crystals are filtered washed with ether

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

実験手順: 8.58 g of N-BOC-cyclopropylamine and 15 g of O-benzyl-3-bromo-1-propanol in 90 ml of DMF are treated at 0°-5° with 2.5 g of sodium hydride (55% in oil). The mixture is stirred at 0°-5° for 1 hour and at room temperature for 3 hours and then treated at 0°-5° with aqueous ammonium chloride solution. The mixture is partitioned in ether/water and the ether phases are washed with water, then dried and concentrated. After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane. After concentration, the residue is crystallized in ether. The crystals are filtered and washed with ether. There are obtained 9.0 g of (3-benzyloxy-propyl)-cyclopropyl-amine hydrochloride, MS (EI): 206 (M+H). The mixture is partitioned in ether/water the ether phases are washed with water dried concentrated After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane After concentration the residue is crystallized in ether The crystals are filtered washed with ether

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Nitrosonium tetrafluoroborate (2.415 g, 20.67 mmol) was added in several portions to a cooled (−30° C.) solution of 1,1-dimethylethyl cyclopropylcarbamate (2.5 g, 15.90 mmol) in anhydrous Pyridine (4 mL) and Acetonitrile (40 mL). The solution was stirred at −30° C. for 30 minutes then at 0° C. for 2 hours. Ice water and EtOAc were added. The organic phase was separated and washed with 1N HCl, 1N NaHCO3, brine, dried over MgSO4, filtered and concentrated in vacuo. The product was collected as 2.66 g. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.37-0.79 (m, 4 H), 1.64 (s, 9 H), 2.18-2.41 (m, 1 H). at 0° C. for 2 hours The organic phase was separated washed with 1N HCl, 1N NaHCO3, brine dried over MgSO4 filtered concentrated in vacuo The product was collected as 2.66 g

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

実験手順: 8.58 g of N-BOC-cyclopropylamine and 15 g of O-benzyl-3-bromo-1-propanol in 90 ml of DMF are treated at 0°-5° with 2.5 g of sodium hydride (55% in oil). The mixture is stirred at 0°-5° for 1 hour and at room temperature for 3 hours and then treated at 0°-5° with aqueous ammonium chloride solution. The mixture is partitioned in ether/water and the ether phases are washed with water, then dried and concentrated. After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane. After concentration, the residue is crystallized in ether. The crystals are filtered and washod with ether. There are obtained 9.0 g of (3-benzyloxy-propyl)-cyclopropyl-amine hydrochloride, MS (EI): 206 (M+H). The mixture is partitioned in ether/water the ether phases are washed with water dried concentrated After chromatography over silica gel with ether/hexane (1:4), the 11.5 g of product are stirred with 120 ml of 4.8 molar hydrochloric acid in dioxane After concentration the residue is crystallized in ether The crystals are filtered

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

実験手順: A solution of cyclopropyl-carbamic acid tert-butyl ester (4.8 g, 30.5 mmol) and pyridine (5.9 mL, 73 mmol) in acetonitrile (75 mL) was cooled to approximately −25° C. in a carbon tetrachloride/dry ice bath. Nitrosonium tetrafluoroborate (4.7 g, 40.2 mmol) was added over a period of 20 min. The cooling bath was removed and the reaction mixture was stirred in an ice-bath at 0° C. for 2.5 h. Water (100 mL) and ethyl acetate (500 mL) were added and the organic layer was washed with water (100 mL), 2 M aqueous HCl (50 mL) and brine (100 mL), dried (magnesium sulfate), filtered, evaporated, and purified in two batches using an ISCO 120 g column, eluting with 10-30% ethyl acetate, to give N-nitroso-N-cyclopropyl-carbamic acid tert-butyl ester (1.5 g, 26%) as a yellow oil. The cooling bath was removed Water (100 mL) and ethyl acetate (500 mL) were added the organic layer was washed with water (100 mL), 2 M aqueous HCl (50 mL) and brine (100 mL) dried (magnesium sulfate) filtered evaporated purified in two batches eluting with 10-30% ethyl acetate