Acetic Acid → HCID 67187742, compound

Temperature

0 °C

To a cooled solution of 5.54 ml (80 mmol) of cyclopropylamine and 2.86 ml (50 mmol) of acetic acid, together with 5 g of 3 Å molecular sieves, in 100 ml of methanol, are added 5 g (20 mmol) of 4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]butan-2-one. The reaction mixture is stirred for 3.5 hrs at reflux. The reaction mixture is then cooled to 0° C. and 1.88 g (30 mmol) of sodium cyanoborohydride are slowly added and the reaction mixture is further stirred for 2 hrs at reflux. The cooled reaction mixture is then filtered over a cake of diatomaceous earth. The cake is washed twice by 80 ml of methanol and the combined methanolic extracts are concentrated under vacuum. 100 ml of water are then added to the residue and the pH is ajusted to 10 with a 1 N solution of sodium hydroxyde. The watery layer is extracted twice with ethyl acetate (2×50 ml). The combined organic layers are washed twice by brine and dried over magnesium sulfate to yield after concentration 5.02 g of a brown oil. Column chromatography (gradient heptane/ethyl acetate) yielded 3 g (51% yield) of N-{4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]butan-2-yl}cyclo-propanamine as a light-brown oil (M+H=293).

1. temperatureat reflux
2. stirringthe reaction mixture is further stirred for 2 hrs
3. temperatureat reflux
4. customThe cooled reaction mixture
5. filtrationis then filtered over a cake of diatomaceous earth
6. washThe cake is washed twice by 80 ml of methanol
7. concentrationthe combined methanolic extracts are concentrated under vacuum
8. addition100 ml of water are then added to the residue
9. extractionThe watery layer is extracted twice with ethyl acetate (2×50 ml)
10. washThe combined organic layers are washed twice by brine
11. dry with materialdried over magnesium sulfate
12. customto yield after concentration 5.02 g of a brown oil

ORD record

ord-c5c9b880466b4925ac2858dafc9eccdc

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927581B2