1-(2-phenylmethoxyethyl)cyclopropan-1-amine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(benzyloxy)propanenitrile (16.9 g 105 mmol) in diethyl ether (400 mL) were added titanium isopropoxide (35.7 mL, 115 mmol) and ethyl magnesium bromide (210 mL, 1 M in diethyl ether) successively at room temperature. After being stirred for 0.5 hour, boron trifluoride etherate (27 mL, 525 mmol) was added. After stirring for another 0.5 hour, 10% aqueous solution of sodium hydroxide (ca. 5.5 mL) was introduced to the above mixture. The resulting mixture was acidified with 1N hydrochloric acid to pH 3, and then washed with dichloromethane. The aqueous layer was basified with 5% aqueous solution of sodium hydroxide to pH 8˜9 and extracted with dichloromethane (100 mL). The organic layer was washed with brine (100 mL), dried over sodium sulfate and concentrated in vacuo to afford 11 g of 1-[2-(benzyloxy)ethyl]cyclopropanamine (yield was 55%). After stirring for another 0.5 hour washed with dichloromethane extracted with dichloromethane (100 mL) The organic layer was washed with brine (100 mL) dried over sodium sulfate concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of the compound (24.7 g) obtained in step (1) above, tetraisopropyl orthotitanate (49.4 mL) and methoxycyclopentane (306 mL), ethyl magnesium bromide (about 3 mol/L, solution in diethyl ether, 102 mL) was added at 0° C. and thereafter the mixture was stirred at room temperature for 3 hours. After adding boron trifluoride/diethylether complex (38.8 mL) at 0° C., the mixture was stirred at room temperature for 1.5 hours. After adding water at 0° C., pH was adjusted to 12 by adding a solution of 10% sodium hydroxide in water. The reaction mixture was extracted with chloroform three times. The combined organic layers were washed with saturated brine and then passed through a phase separator and concentrated under reduced pressure. The resulting residue was purified by NH silica gel column chromatography (n-hexane:ethyl acetate=100:0-5:95) and further purified by silica gel column chromatography (n-hexane:ethylacetate=90:10-5:95, then chloroform:methanol=100:0-90:10) to give 1-[2-(benzyloxy)ethyl]cyclopropaneamine as a pale yellow oil (12.5 g). was added at 0° C. After adding boron trifluoride/diethylether complex (38.8 mL) at 0° C. the mixture was stirred at room temperature for 1.5 hours The reaction mixture was extracted with chloroform three times The combined organic layers were washed with saturated brine concentrated under reduced pressure The resulting residue was purified by NH silica gel column chromatography (n-hexane:ethyl acetate=100:0-5:95) further purified by silica gel column chromatography (n-hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-(benzyloxy)propanenitrile (16.9 g 105 mmol) in diethyl ether (400 mL) were added titanium isopropoxide (35.7 mL, 115 mmol) and ethyl magnesium bromide (210 mL, 1 M in diethyl ether) successively at room temperature. After being stirred for 0.5 hour, boron trifluoride etherate (27 mL, 525 mmol) was added. After stirring for another 0.5 hour, 10% aqueous solution of sodium hydroxide (ca. 5.5 mL) was introduced to the above mixture. The resulting mixture was acidified with 1N hydrochloric acid to pH 3, and then washed with dichloromethane. The aqueous layer was basified with 5% aqueous solution of sodium hydroxide to pH 8˜9 and extracted with dichloromethane (100 mL). The organic layer was washed with brine (100 mL), dried over sodium sulfate and concentrated in vacuo to afford 11 g of 1-[2-(benzyloxy)ethyl]cyclopropanamine (yield was 55%). After stirring for another 0.5 hour washed with dichloromethane extracted with dichloromethane (100 mL) The organic layer was washed with brine (100 mL) dried over sodium sulfate concentrated in vacuo