Borane → N-[(5-chloro-2-methylphenyl)methyl]cyclopropanamine

At 0° C., a suspension of 5-chloro-N-cyclopropyl-2-methylbenzamide (1 eq.) from the previous step in THF (0.4 M) was added borane (1.0 M in THF, 3 eq.). The resulting suspension was warmed to RT over 1 h and then heated at reflux for 1 h. The now pale yellow solution was re-cooled to 0° C. and carefully quenched with 1 N aq. HCl. The resulting mixture was heated at reflux for 1 h to ensure complete breakdown of the amine-borane complex. Following careful neutralization with 1 N aq. NaOH, the aqueous layer was separated and back extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and the crude product thus obtained was purified further by way of flash chromatography (SiO2, Hex→4:1 (v/v) Hex:Et2O) to reveal the title compound as a colorless oil.

1. temperatureheated
2. temperatureat reflux for 1 h
3. temperatureThe now pale yellow solution was re-cooled to 0° C.
4. customcarefully quenched with 1 N aq. HCl
5. temperatureThe resulting mixture was heated
6. temperatureat reflux for 1 h
7. customthe aqueous layer was separated
8. extractionback extracted with EtOAc
9. washThe combined organic extracts were washed with brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-839be04a566443ca8d30e5e60d8544b2

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889714B2