Reacción #90764

Ecuación de reacción

2,5-dichloro-4-iodopyridine

2-aminobenzoic acid

DPEPhos

K3PO4

→

title compound

Rendimiento 73.0%

2-[(2,5-Dichloro-4-pyridinyl)amino]benzoic acid

Rendimiento 73.0%

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas degassed
2. 2
   workup.WAITleft
3. 3
   workup.ADDITIONAdded another 160 mg of Pd(OAc)2 to the mixture
4. 4
   Temperaturaheated to 120° C. for another 24 h
5. 5
   TemperaturaThe mixture was cooled to room temperature
6. 6
   Filtraciónfollowed by filtration
7. 7
   Lavadowashing with EtOAc
8. 8
   Filtraciónfollowed by filtration
9. 9
   Otrocollected solids could not
10. 10
    Otrobe dried completely
11. 11
    FiltraciónThe resulting paste was filtered
12. 12
    Lavadowashed with water and TBME
13. 13
    SecadoThe solid was dried under vacuum over P2O5 for 2 days

Procedimiento

A mixture of 2,5-dichloro-4-iodopyridine (10 g, 36.5 mmol), 2-aminobenzoic acid (4.85 g, 35.4 mmol), DPEPhos [bis(2-diphenylphosphinophenyl)ether] (1.6 g, 2.97 mmol), palladium(II) acetate (160 mg, 0.713 mmol) and K3PO4 (20 g, 94 mmol) was degassed and heated at 120° C. (oil bath temp) for 20 h. After 20 h, LCMS showed there was 33% (relative to the desired product) starting material left. Added another 160 mg of Pd(OAc)2 to the mixture, and heated to 120° C. for another 24 h. LCMS showed conversion complete. The mixture was cooled to room temperature, followed by filtration, and washing with EtOAc. The solids were acidified to pH=7-8, followed by filtration. However, the mixture was a paste, and collected solids could not be dried completely. The solids (11 g) was acidified with 6N HCl to pH=1. The resulting paste was filtered, and washed with water and TBME. The solid was dried under vacuum over P2O5 for 2 days to give the title compound (7.32 g, 60.2% yield). MS: M(C12H8Cl2N2O2)=283.11, (M+H)+=283.8; 1H NMR (400 MHz, DMSO) ppm 13.6 (s, 1 H) 10.2 (s, 1 H) 8.3 (s, 1 H) 8.0 (d, 1 H) 7.6 (q, 2 H) 7.3 (s, 1 H) 7.2 (m, 1 H).

Fuente