Sodium Hydroxide → 1-[2-(benzyloxy)ethyl]cyclopropan-1-amine

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).

1. additionwas added at 0° C.
2. additionAfter adding boron trifluoride/diethylether complex (38.8 mL) at 0° C.
3. stirringthe mixture was stirred at room temperature for 1.5 hours
4. extractionThe reaction mixture was extracted with chloroform three times
5. washThe combined organic layers were washed with saturated brine
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified by NH silica gel column chromatography (n-hexane:ethyl acetate=100:0-5:95)
8. customfurther purified by silica gel column chromatography (n-hexane

ORD record

ord-9b544eb58a1a4eb180a31f43c3b2f722

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09422240B2