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

HRID 1158578노트

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HRID 1158578 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

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

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온도
70 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-ac5f605e2c994c59b9e9e95613497330
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07811595B2

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