Phenylurea → 1-(4-Methylphenyl)-3-phenylurea

In a nitrogen-atmosphere glovebox, a microwave vial equipped with a magnetic stir bar was charged with phenylurea (100 mg, 0.734 mmol, 1 equivalent), potassium phosphate (234 mg, 1.10 mmol, 5 equivalents), tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3) (6.7 mg, 0.00734 mmol, 0.01 equivalents) and phosphine ligand (0.029 mmol, 0.04 equivalents). Then 1,2-dimethoxyethane (1.34 mL) was syringed into the vial. After stirring the mixture for 1 hour at room temperature, 4-chlorotoluene (96 μL, 0.808 mmol, 1.1 equivalents) was added. The vial was sealed with a crimp top and placed in a heating block at 85 ° C. After 15 hours, the reaction vial was cooled to room temperature and brought out of the glovebox. The reaction solution was diluted with dimethylformamide (0.6 mL) and stirred for 15 minutes. The slurry was then filtered through a pad of diatomaceous earth. The vial was rinsed with dimethylformamide (0.6 mL) before passing through the filter. The combined filtrate was concentrated on a rotary evaporator to furnish an orange oil. A 1:1 mixture of methanol:water (3.5 mL) was added dropwise to the crude concentrate, leading to the precipitation of product. The solids were collected by filtration and washed with 1:1 methanol:water (3 mL). The isolated product urea was drie rn a vacuum oven for 6 hours at 60 ° C./150 mm Hg. (literature reference: Kotecki BJ, et al. Org. Lett. 2009; 11: 947-950). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.52 (t, J=22.7 Hz, 2H), 7.42 (dd, J=8.5, 1.0 Hz, 2H), 7.31 (t, J=5.4 Hz, 2H), 7.26 (dd, J=10.7, 5.2 Hz, 2H), 7.07 (d, J=8.2 Hz, 2H), 6.95 (dd, J=10.5, 4.2 Hz, 1H), 2.24 (s, 3H).

1. customIn a nitrogen-atmosphere glovebox, a microwave vial equipped with a magnetic stir bar
2. customThe vial was sealed with a crimp top
3. customplaced in a heating block at 85 ° C
4. waitAfter 15 hours
5. customthe reaction
6. temperaturevial was cooled to room temperature
7. stirringstirred for 15 minutes
8. filtrationThe slurry was then filtered through a pad of diatomaceous earth
9. washThe vial was rinsed with dimethylformamide (0.6 mL)
10. concentrationThe combined filtrate was concentrated on a rotary evaporator
11. customto furnish an orange oil
12. concentrationconcentrate
13. customleading to the precipitation of product
14. filtrationThe solids were collected by filtration
15. washwashed with 1:1 methanol
16. customfor 6 hours
17. customat 60 ° C.

ORD-Eintrag

ord-32b6625deb514448a4d7dbc179786305

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09200021B2