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

HRID 1430197ノート

反応式

HRID 1430197 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

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

反応条件

温度
70 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-62c79fcf321e4b84b921fa2bc1c295f1
出典データセット
uspto-grants-2015_01
特許番号
US08940773B2

反応ノート

読み込み中…