Acetic Acid → (1R,2S)-Tranylcypromine

Temperature

0 °C

Cyclopropyl amine (12.4 mL, 185 mmol) was added to a solution of the ketone prepared above (27.0 g, 123 mmol) in dichloroethane (600 mL) and acetic acid (14.0 mL, 246 mmol). The reaction mixture was cooled to 0° C. and NaBH(OAc)3 (52 g, 246 mmol) was added protionwise. After being stirred for 2.75 h at 23° C., the reaction was re-cooled to 0° C. and quenched with 1 M NaOH (200 mL). The aqueous layer was extracted with CH2Cl2 (2×200 mL) and the combined organic layers were washed with brine (300 mL), dried with MgSO4, filtered, and concentrated in vacuo. The crude mixture of cis and trans amines was purified by flash column chromatography 75% EtOAc/hexanes (2.5% TEA)→100% EtOAc (2.5% TEA)→10% MeOH/CH2Cl2 (1% NH4OH) to provide the trans amine as an off-white solid.

1. temperaturethe reaction was re-cooled to 0° C.
2. customquenched with 1 M NaOH (200 mL)
3. extractionThe aqueous layer was extracted with CH2Cl2 (2×200 mL)
4. washthe combined organic layers were washed with brine (300 mL)
5. dry with materialdried with MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. additionThe crude mixture of cis and trans amines
9. customwas purified by flash column chromatography 75% EtOAc/hexanes (2.5% TEA)

ORD record

ord-372a568d3cc34b39a6550ba8a8162804

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772296B2