Ethyl chloroformate → trans-2,2-Dimethyl-3-phenyl-cyclopropylamine

Temperature

100 °C

To a solution of trans-2,2-dimethyl-3-phenyl-cyclopropanecarboxylic acid (1.78 g, 9.4 mmol) in acetone was added water (4 mL) followed, at −5° C., by ethyl chloroformate (0.982 mL, 10.34 mmol). The reaction mixture was stirred for 20 minutes and then a solution of sodium azide (731 mg, 11.28 mmol) in water (8 mL) was added. The resulting mixture was stirred for 45 minutes and then diluted with a 1:1 mixture of water and toluene. The organic layer was separated, dried over Na2SO4, filtered and heated at 100° C. for 1 hour. The solvent was then removed under reduced pressure and an aqueous solution of HCl (8 M, 30 mL) was added, and the resulting mixture was heated at reflux for 45 minutes. The reaction mixture was cooled and an aqueous solution of HCl (10%) was added; the resulting mixture was washed with ethyl ether, then basified by addition of NaOH. The resulting mixture was extracted with ethyl ether, and the combined organic extracts were dried over Na2SO4, filtered, and evaporated under reduced pressure to give 1.05 g (70% yield) of trans-2,2-dimethyl-3-phenyl-cyclopropylamine.

1. stirringThe resulting mixture was stirred for 45 minutes
2. customThe organic layer was separated
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. customThe solvent was then removed under reduced pressure
6. additionan aqueous solution of HCl (8 M, 30 mL) was added
7. temperaturethe resulting mixture was heated
8. temperatureat reflux for 45 minutes
9. temperatureThe reaction mixture was cooled
10. additionan aqueous solution of HCl (10%) was added
11. washthe resulting mixture was washed with ethyl ether
12. additionbasified by addition of NaOH
13. extractionThe resulting mixture was extracted with ethyl ether
14. dry with materialthe combined organic extracts were dried over Na2SO4
15. filtrationfiltered
16. customevaporated under reduced pressure

ORD record

ord-2d6e2c09f7204126a5f5d4e70d3cc4bb

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07723391B2