Ammonium Chloride → 3-Bromo-N2-cyclopropyl-4-fluorobenzene-1,2-diamine

To a solution of 2-bromo-1,3-difluoro-4-nitrobenzene (1.19 g, 5.0 mmol) in MeCN (10 mL) were added DIPEA (1.74 mL, 10.0 mmol) and cyclopropylamine (360 mL, 5.17 mmol). The reaction mixture was stirred at RT for 4 h. The volatiles were removed under reduced pressure and the resulting residue was partitioned between DCM and water. The organic fraction was dried, concentrated in vacuo and the resulting residue taken up in a 3:1 mixture of MeOH:water (40 mL). NH4Cl (1.53 g, 28.6 mmol) and iron powder (1.06 g, 4.76 mmol) were added and the reaction mixture heated at 80° C. for 3 h. After cooling to RT, the mixture was filtered through a pad of Celite® and washed with additional MeOH. The filtrate was concentrated in vacuo and the resulting residue partitioned between DCM and an aqueous solution of NaHCO3. The organic fraction was dried and concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-5% MeOH in EtOAc) to afford the title compound as a brown oil (759 mg, 62% over 2 steps). LCMS (Method C): RT 2.97 min [M+H]+ 245.02

1. customThe volatiles were removed under reduced pressure
2. customthe resulting residue was partitioned between DCM and water
3. customThe organic fraction was dried
4. concentrationconcentrated in vacuo
5. additionthe resulting residue taken up in a 3:1 mixture of MeOH
6. temperaturethe reaction mixture heated at 80° C. for 3 h
7. temperatureAfter cooling to RT
8. filtrationthe mixture was filtered through a pad of Celite®
9. washwashed with additional MeOH
10. concentrationThe filtrate was concentrated in vacuo
11. customthe resulting residue partitioned between DCM
12. customThe organic fraction was dried
13. concentrationconcentrated in vacuo
14. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-5% MeOH in EtOAc)

ORD record

ord-d2d893eaeee54b598054e245e7a07920

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2