Reacción #166171

Ecuación de reacción

4-chlorotoluene

phenylurea

potassium phosphate

phosphine

→

1-Phenyl-3-p-tolylurea

Disolventes

water

methanol

1,2-dimethoxyethane

dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroIn a nitrogen-atmosphere glovebox, a microwave vial equipped with a magnetic stir bar
2. 2
   OtroThe vial was sealed with a crimp top
3. 3
   Otroplaced in a heating block at 85° C
4. 4
   workup.WAITAfter 15 hours
5. 5
   Otrothe reaction
6. 6
   Temperaturavial was cooled to room temperature
7. 7
   workup.STIRRINGstirred for 15 minutes
8. 8
   FiltraciónThe slurry was then filtered through a pad of diatomaceous earth
9. 9
   LavadoThe vial was rinsed with dimethylformamide (0.6 mL)
10. 10
    ConcentraciónThe combined filtrate was concentrated on a rotary evaporator
11. 11
    Otroto furnish an orange oil
12. 12
    Concentraciónconcentrate
13. 13
    Otroleading to the precipitation of product
14. 14
    FiltraciónThe solids were collected by filtration
15. 15
    Lavadowashed with 1:1 methanol
16. 16
    SecadoThe isolated product urea was dried in a vacuum oven for 6 hours at 60° C./150 mm Hg

Procedimiento

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, 1.5 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 dried in a vacuum oven for 6 hours at 60° C./150 mm Hg. (literature reference: Kotecki B J, 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).

Fuente