Methanol → [(4-(4-Methylphenyl)pyridine-2-carbonyl)amino]-acetic acid methyl ester

HRID 1024522Notes

Reaction equation

HRID 1024522 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][NH:5][C:6]([C:8]1[CH:13]=[C:12](I)[CH:11]=[CH:10][N:9]=1)=[O:7].CO.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:15])[CH2:4][NH:5][C:6]([C:8]1[CH:13]=[C:12]([C:30]2[CH:31]=[CH:32][C:27]([CH3:26])=[CH:28][CH:29]=2)[CH:11]=[CH:10][N:9]=1)=[O:7]

Participants

7

Reactant 4

HCID 887MethanolHCID 62657Potassium Phosphate, TribasicHCID 79799Tolylboronic acidHCID 59513095[(4-Iodo-pyridine-2-carbonyl)amino]-acetic acid methyl ester

Product 1

HCID 24891097[(4-(4-Methylphenyl)pyridine-2-carbonyl)amino]-acetic acid methyl esterYield 85%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

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]+.

Workup

  1. customThe solvents are then removed under reduced pressure
  2. customthe solid which remains is partitioned between CH2Cl2 and 1M K2CO3
  3. customThe aqueous phase is removed
  4. washthe organic phase washed with H2O, sat. NaCl
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material is purified over silica (EtOAc:heptane gradient 1:4 to 3:7)

Sources & evidence

ORD record
ord-ad8513d4395d43a2ab12eb5811a98c7c
Source dataset
uspto-grants-2014_05
Patent number
US08722895B2

Reaction notes

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