Reaction #2275698

Reaction equation

[(3-hydroxy-5-trifluoromethane-sulfonyloxy-pyridine-2-carbonyl)-amino]-acetic acid methyl ester

3-chlorophenylboronic acid

K3PO4

→

desired compound

Yield 53.0%

{[5-(3-chloro-phenyl)-3-hydroxy-pyridine-2-carbonyl]-amino}-acetic acid methyl ester

Yield 53.0%

Solvents

1,4-dioxane

Conditions

Workup

1. 1
   TemperatureAfter this time, the mixture is cooled to room temperature
2. 2
   Concentrationconcentrated under reduced pressure
3. 3
   workup.ADDITIONThe residue is then treated with 1M HCl (1 mL)
4. 4
   workup.ADDITIONdiluted with EtOAc
5. 5
   OtherThe organic layer is separated
6. 6
   Washwashed with H2O, saturated aqueous NaCl
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   OtherThe crude material is purified over silica (EtOAc:heptane 3:7)
9. 9
   OtherThe resulting solid can be crystallized from EtOAc/heptane

Procedure

To a degassed solution of [(3-hydroxy-5-trifluoromethane-sulfonyloxy-pyridine-2-carbonyl)-amino]-acetic acid methyl ester, 5, (0.30 g, 0.84 mmol) in 1,4-dioxane (10 mL) at room temperature under N2 is added 3-chlorophenylboronic acid (0.196 g, 1.26 mmol), Pd(dppf)Cl2 (0.068 g, 0.0084 mmol) and K3PO4 (0.195 g, 0.92 mmol). The resulting suspension is heated in a sealed tube at 85° C. for 16 hours. After this time, the mixture is cooled to room temperature and concentrated under reduced pressure. The residue is then treated with 1M HCl (1 mL) and diluted with EtOAc. The organic layer is separated, washed with H2O, saturated aqueous NaCl and concentrated under reduced pressure. The crude material is purified over silica (EtOAc:heptane 3:7). The resulting solid can be crystallized from EtOAc/heptane to afford 0.143 g (53% yield) of the desired compound as a colorless solid. 1H NMR (400 MHz, CDCl3) δ ppm 11.77 (1H, s), 8.36 (1H, t, J=5.7 Hz), 8.24 (1H, d, J=1.8 Hz), 7.50-7.53 (1H, m), 7.39-7.42 (2H, m), 7.34-7.37 (2H, m), 4.20 (2H, d, J=5.9 Hz), 3.76 (3H, s). HPLC-MS: m/z.

Source