Boron trifluoride etherate → 1-(2-(Benzyloxy)phenyl)cyclopropanamine

Temperature

-78 °C

Titanium(IV) isopropoxide (1.62 mL) was added to a stirred solution of 2-(benzyloxy)benzonitrile (1.05 g) in diethyl ether (25 mL) cooled to −78° C. under N2 followed by the dropwise addition of ethylmagnesium bromide (3.67 mL of a 3M solution in diethylether). The resulting mixture was stirred at −78° C. for 10 min and then warmed to rt over 1 h. Boron trifluoride diethyl etherate (1.27 mL) was added dropwise and the mixture was stirred for 1 h. The reaction was quenched with 1M HCl (30 mL). Diethyl ether (30 mL) was added and the organic layer separated. To the aqueous layer was added aqueous 10% NaOH (50 mL) and diethyl ether and this was filtered through celite to remove solids (which were washed with further diethyl ether). This mixture was extracted with diethyl ether (2×70 mL) and dichloromethane (70 mL). All the organic layers were combined, dried (Na2SO4) and the solvents removed in vacuo. The residue was dissolved in dichloromethane and loaded on to an 10 g SCX cartridge. The impurities were washed through with methanol (50 mL) and discarded. Elution with 7N methanolic ammonia (25 mL) and evaporation in vacuo gave the subtitle compound as a brown oil (0.625 g).

1. temperaturewarmed to rt over 1 h
2. stirringthe mixture was stirred for 1 h
3. customThe reaction was quenched with 1M HCl (30 mL)
4. additionDiethyl ether (30 mL) was added
5. customthe organic layer separated
6. additionTo the aqueous layer was added aqueous 10% NaOH (50 mL) and diethyl ether
7. filtrationthis was filtered through celite
8. customto remove
9. washsolids (which were washed with further diethyl ether)
10. extractionThis mixture was extracted with diethyl ether (2×70 mL) and dichloromethane (70 mL)
11. dry with materialdried (Na2SO4)
12. customthe solvents removed in vacuo
13. dissolutionThe residue was dissolved in dichloromethane
14. washThe impurities were washed through with methanol (50 mL)
15. washElution
16. customwith 7N methanolic ammonia (25 mL) and evaporation in vacuo

ORD record

ord-9faeefd2226a4d8d8668640d0e0ca9f8

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889692B2