Boron trifluoride etherate → 1-(3-Chlorophenyl)cyclopropanamine

Temperature

-78 °C

To a solution of 3-chlorobenzonitrile (1 g, 7.27 mmol) and titanium (IV) isopropoxide (2.34 mL, 8 mmol) in Et2O (35 mL) at −78° C. was added ethyl magnesium chloride in THF (5.71 mL, 15.99 mmol). The solution was stirred for 10 min at −78° C. then at 25° C. for 1 h. BF3.Et2O (1.82 mL, 14.54 mmol) was added and the solution was stirred for 1 h at 25° C. The reaction mixture was quenched with 1N HCl (22 mL) Et2O was added (100 mL). Then 10% aq. NaOH (70 mL) was added and the layers were separated. The organic layer was dried over Na2SO4, filtered and concentrated. The crude residue was purified by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 5% CH3CN/H2O 2.5 min, 5-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min) to give after lyophilization of the purified fractions the title compound. MS (UPLC-MS): 170 [M+H]+, 168 [M−H]−; tR (HPLC conditions f): 1.22 min.

1. waitat 25° C. for 1 h
2. stirringthe solution was stirred for 1 h at 25° C
3. customThe reaction mixture was quenched with 1N HCl (22 mL) Et2O
4. additionwas added (100 mL)
5. additionThen 10% aq. NaOH (70 mL) was added
6. customthe layers were separated
7. dry with materialThe organic layer was dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude residue was purified by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 5% CH3CN/H2O 2.5 min, 5-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min)

ORD record

ord-0d821cb87d224c9381604e6e662de211

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085555B2