Formic Acid → 4-Bromo-N,3-dimethylbenzenamine

Temperature

0 °C

A solution of 4-bromo-3-methylaniline (3.72 g, 20 mmol) in formic acid (15 mL) was heated at 100° C. for 8 h. The solvent was removed in vacuo and the residue was partitioned between EtOAc (100 mL) and aq NaHCO3 (50 mL). The layers were separated and the organic layers was dried (Na2SO4) and concentrated. The residue was dissolved in THF (80 mL) and cooled to 0° C. Lithium aluminum hydride (1.52 g, 40 mmol) was added portionwise over 10 min. The mixture was stirred at rt for 8 h and an additional equivalent (750 mg) of LAH was added. After 16 h, the mixture was quenched with EtOAc and MeOH and the solids were filtered. The material was purified by SiO2 flash column chromatography to yield the title compound (2.56 g, 64%) as a colorless oil. 1H-NMR (CDCl3): δ 7.29 (d, 1H, J=8.6 Hz), 6.33 (dd, 1H, J=2.8 Hz), 7.29 (d, 1H, J=2.8, 8.6 Hz), 3.66 (s, 2H), 2.81 (d, 1H, J=5.4 Hz), 2.33 (s, 3H).

1. customThe solvent was removed in vacuo
2. customthe residue was partitioned between EtOAc (100 mL) and aq NaHCO3 (50 mL)
3. customThe layers were separated
4. dry with materialthe organic layers was dried (Na2SO4)
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in THF (80 mL)
7. waitAfter 16 h
8. customthe mixture was quenched with EtOAc and MeOH
9. filtrationthe solids were filtered
10. customThe material was purified by SiO2 flash column chromatography

ORD record

ord-bef6fecd0cbb4ff68b5b679866dc508d

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07138530B2