Methane → (2-Chloro-6-fluorophenyl)-P-tolyl-amine

Temperature

25 °C

A mixture of 2-chloro-6-fluoroaniline (4.00 g, 27.5 mmol), 4-bromotoluene (4.70 g, 27.5 mmol), sodium tert-butylate (4.75 g, 49.4 mmol), and toluene (55 mL) is stirred at 25° C. under nitrogen for 30 minutes. To this mixture, a solution of palladium-bis-(dibenzylidenacetone) (15.8 mg, 55 mmol) and tri-tert-butylphosphine (1) (8.3 mg, 0.04 mmol) in toluene (5 mL) is added and the resulting suspension is stirred at 110° C. for 14 hours. The mixture is then cooled to 30° C. Water (30 ml), concentrated hydrochloric acid (10 ml), charcoal and cellite (1 g each) are added and stirring is continued for 1 hour. The mixture is filtered and the filtrate is separated into its phases. The organic phase is washed three times with water (10 mL) and concentrated in vacuo to give 6.5 g of crude (2′-chloro-6′-fluorophenyl)-(4-methylphenyl)-amine. The product can be used directly in the next step (Step 1.2). Alternatively, it can be distilled in vacuo by Kugelrohr.

1. stirringthe resulting suspension is stirred at 110° C. for 14 hours
2. temperatureThe mixture is then cooled to 30° C
3. stirringstirring
4. waitis continued for 1 hour
5. filtrationThe mixture is filtered
6. customthe filtrate is separated into its phases
7. washThe organic phase is washed three times with water (10 mL)
8. concentrationconcentrated in vacuo

ORD record

ord-7ade99b1b35c4155a140400e94e431f8

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07402603B2