Ammonium formate → 2-Bromo-5-chloroaniline

Temperature

50 °C

1-Bromo-4-chloro-2-nitrobenzene (140 g, 0.59 mol) was dissolved in 2.5 L of MeOH with gentle heating (50° C.) in a hot water bath. A solution of ammonium formate (303 g, 4.81 mol) in 500 mL of water was added. Zinc powder (155 g, 2.36 mol) was added in small portions, resulting in heat evolution and refluxing of the solvent. Subsequent additions were made cautiously as to avoid build up of excess unreacted zinc. The reaction was cooled to room temperature and filtered through a large plug of CELITE® filter aid. The filtrate was then concentrated until a biphasic mixture of red oil and water was evident. The product was extracted with five 200 mL portions of diethyl ether. The organics were combined and dried over sodium sulfate, decanted, and concentrated in vacuo to a reddish-brown oil. The oil was redissolved in 150 mL of dichloromethane/hexanes and filtered through a plug of silica gel. The filtrate was concentrated to an orange oil. Addition of hexanes (200 mL) and cooling in a dry ice bath resulted in precipitation of 2-bromo-5-chloroaniline as a pale yellow solid (92.1 g, 75%) that was collected via vacuum filtration.

1. customresulting in heat evolution
2. temperaturerefluxing of the solvent
3. temperatureThe reaction was cooled to room temperature
4. filtrationfiltered through a large plug of CELITE®
5. filtrationfilter aid
6. concentrationThe filtrate was then concentrated until a biphasic mixture of red oil and water
7. extractionThe product was extracted with five 200 mL portions of diethyl ether
8. dry with materialdried over sodium sulfate
9. customdecanted
10. concentrationconcentrated in vacuo to a reddish-brown oil
11. dissolutionThe oil was redissolved in 150 mL of dichloromethane/hexanes
12. filtrationfiltered through a plug of silica gel
13. concentrationThe filtrate was concentrated to an orange oil
14. additionAddition of hexanes (200 mL)
15. temperaturecooling in a dry ice bath

ORD record

ord-d1ce18014b2e4545b3b1d93bd518c728

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268859B2