Reaction #2275708

Reaction equation

2-[(3-hydroxy-5-trifluoromethanesulfonyloxy-pyridine-2-carbonyl)-amino]-2-methyl-propionic acid methyl ester

3-chlorophenyl boronic acid

K3PO4

→

desired compound

Yield 73.0%

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

Yield 73.0%

Solvents

1,4-dioxane

Conditions

Workup

1. 1
   TemperatureAfter cooling
2. 2
   Filtrationthe reaction solution is filtered through Celite™
3. 3
   Washthe collected solids are washed with additional MeOH
4. 4
   ConcentrationThe filtrate and washings are concentrated under reduced pressure
5. 5
   workup.DISSOLUTIONthe residue dissolved in CH2Cl2
6. 6
   Washwashed with 10% citric acid
7. 7
   DryingThe organic layer is dried (Na2SO4)
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    OtherThe crude product is purified over silica (EtOAc:heptane 1:4)

Procedure

To a degassed solution of 2-[(3-hydroxy-5-trifluoromethanesulfonyloxy-pyridine-2-carbonyl)-amino]-2-methyl-propionic acid methyl ester (0.17 g, 0.44 mmol) in 1,4-dioxane (3 mL) at room temperature under N2 is added 3-chlorophenyl boronic acid (0.082 g, 0.53 mmol), K3PO4 (0.112 g, 0.53 mmol) and Pd(dppf)Cl2 (0.036 g, 0.04 mmol). The resulting suspension is heated to 85° C. in a sealed tube for 20 hours. After cooling, the reaction solution is filtered through Celite™ and the collected solids are washed with additional MeOH. The filtrate and washings are concentrated under reduced pressure and the residue dissolved in CH2Cl2 and washed with 10% citric acid. The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product is purified over silica (EtOAc:heptane 1:4) to afford 0.112 g (73% yield) of the desired compound as a colorless oil. 1H NMR (250 MHz, CDCl3) δ ppm 11.83 (1H, br s), 8.29 (1H, br s), 8.10 (1H, d, J=2.0 Hz), 7.40 (1H, m), 7.08-7.34 (4H, m), 3.65 (3H, s), 1.55 (6H, s). HPLC-MS: m/z 349 [M+H]+.

Source