Nitric Acid → 4-Aminoindan

Temperature

5 °C

24 ml (349 mmol) 65% nitric acid are cooled to 0-5° C. 28 ml (518.5 mmol) of concentrated sulphuric acid are slowly added dropwise while cooling with ice. This solution is cooled to 5° C. and slowly added dropwise to 30 ml (232 mmol) indane cooled to 0-5° C., with vigorous stirring and further cooling with ice. The reaction mixture is stirred for 30 min at 0-5° C., and then heated to 25° C. for 1 h with stirring. Then the solution is added dropwise to 150 ml ice/water and stirred for 30 min. The aqueous phase is extracted three times with 200 ml diethyl ether. The combined organic phases are washed twice with 200 ml saturated sodium hydrogen carbonate solution and once with 150 ml distilled water. Then the organic phase is dried with MgSO4 and the solvent is eliminated in vacuo. The crude product is dissolved in 250 ml of methanol and combined with 4.5 g Raney nickel. The reaction mixture is hydrogenated for 16 h at 3 bar H2 pressure and 25° C. Then the catalyst is filtered off and the solvent is eliminated in vacuo. The crude product is purified by column chromatography. The carrier used is silica gel and the eluant used is a mixture of cyclohexane:ethyl acetate (75:25).

1. temperaturewhile cooling with ice
2. temperaturecooled to 0-5° C.
3. temperaturefurther cooling with ice
4. stirringThe reaction mixture is stirred for 30 min at 0-5° C.
5. temperatureheated to 25° C. for 1 h
6. stirringwith stirring
7. stirringstirred for 30 min
8. extractionThe aqueous phase is extracted three times with 200 ml diethyl ether
9. washThe combined organic phases are washed twice with 200 ml saturated sodium hydrogen carbonate solution and once with 150 ml
10. distillationdistilled water
11. dry with materialThen the organic phase is dried with MgSO4
12. dissolutionThe crude product is dissolved in 250 ml of methanol
13. filtrationThen the catalyst is filtered off
14. customThe crude product is purified by column chromatography
15. additiona mixture of cyclohexane:ethyl acetate (75:25)

ORD record

ord-fe22c962e86641fe807278f5a29195fa

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07521457B2