Reaction #2275711

Reaction equation

[(4-iodo-pyridine-2-carbonyl)-amino]-acetic acid methyl ester

MeOH

K3PO4

4-methylphenyl boronic acid

→

desired compound

Yield 85.0%

[(4-(4-methylphenyl)pyridine-2-carbonyl)amino]-acetic acid methyl ester

Yield 85.0%

Solvents

1,4-dioxane

Conditions

Workup

1. 1
   OtherThe solvents are then removed under reduced pressure
2. 2
   Otherthe solid which remains is partitioned between CH2Cl2 and 1M K2CO3
3. 3
   OtherThe aqueous phase is removed
4. 4
   Washthe organic phase washed with H2O, sat. NaCl
5. 5
   Dryingdried (MgSO4)
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   OtherThe crude material is purified over silica (EtOAc:heptane gradient 1:4 to 3:7)

Procedure

To a degassed solution of [(4-iodo-pyridine-2-carbonyl)-amino]-acetic acid methyl ester, 23, (0.150, 0.47 mmol) in 1,4-dioxane (4 mL) and MeOH (2 mL) is added K3PO4 (0.109 mg, 0.52 mmol), Pd(dppf)Cl2 (0.038 g, 0.047 mmol) and 4-methylphenyl boronic acid (0.064 g, 0.47 mmol). The reaction is heated to 70° C. in a sealed tube under N2 for 16 hours. The solvents are then removed under reduced pressure and the solid which remains is partitioned between CH2Cl2 and 1M K2CO3. The aqueous phase is removed and the organic phase washed with H2O, sat. NaCl, dried (MgSO4), filtered and concentrated under reduced pressure. The crude material is purified over silica (EtOAc:heptane gradient 1:4 to 3:7) to afford 0.113 g (85% yield) of the desired compound. 1H NMR (400 MHz, CDCl3) δ ppm 8.60 (1H, dd, J=5.1, 0.7 Hz), 8.55 (1H, t, J=4.8 Hz), 8.43-8.44 (1H, m), 8.43 (1H, s), 7.66 (1H, dd, J=5.1, 1.8 Hz), 7.63 (2H, d, J=8.4 Hz), 7.32 (2H, d, J=8.1 Hz), 4.31 (1H, d, J=5.9 Hz), 3.81 (2H, s), 2.43 (3H, s). HPLC-MS: m/z 285 [M+H]+.

Source