Diethyl Ether → 3-(3-ethoxy-4-methoxyphenyl)-N-methoxy-3-(1-oxoisoindolinyl)-propionamide

HRID 431103

反応式

HRID 431103 の反応式
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]2=[O:26])[CH2:13][C:14]([OH:16])=O)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].Cl.[CH3:28][O:29][NH2:30].CN1CCCCC1.CCOCC>C(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:17]2[CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]2=[O:26])[CH2:13][C:14]([NH:30][O:29][CH3:28])=[O:16])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]

参加物

6

反応物 4

HCID 3283Diethyl EtherHCID 12291N-MethylpiperidineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 183492403-(3-Ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolinyl)propanoic acid

生成物 1

HCID 99299653-(3-ethoxy-4-methoxyphenyl)-N-methoxy-3-(1-oxoisoindolinyl)-propionamide収率 67%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of 3-(3-ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolinyl)propanoic acid (500 mg, 1.41 mmol) and N,N′-carbonyldiimidazole (250 mg, 1.54 mmol) in methylene chloride (30 mL) under nitrogen was stirred at room temperature for 30 minutes. To the solution was added O-methyl hydroxylamine hydrochloride (175 mg, 2.09 mmol) followed by the addition of 1-methyl piperidine (0.26 mL, 2.14 mmol). The mixture was stirred at room temperature for 2 hours and then was heated to reflux for 14 hours. The cooled reaction mixture was washed with hydrochloric acid (1N, 25 mL), saturated sodium bicarbonate (25 mL), brine (25 mL), and then dried over sodium carbonate and sodium sulfate. Removal of solvent in vacuo gave a solid which was stirred with ether (10 mL) for 30 minutes. This suspension was filtered and the solid was washed with ether (2×10 mL) to give 3-(3-ethoxy-4-methoxyphenyl)-N-methoxy-3-(1-oxoisoindolinyl)-propionamide as a white solid (360 mg, 67% yield): mp, 138.0-139.5° C.; 1H NMR (CDCl3) δ1.41 (t, J=6.9 Hz, 3H, CH3), 2.95 (dd, J=4.6, 14.5 Hz, 1H, CHH), 3.53 (dd, J=11.2, 14.5 Hz, 1H, CHH), 3.62 (s, 3H, CH3), 3.84 (s, 3H, CH3), 4.02 (q, J=6.9 Hz, 2H, CH2), 4.23 (d, J=17.1 Hz, 1H, NCHH), 4.46 (d, J=17 Hz, 1H, NCHH), 5.49 (dd, J=4.4, 10.3 Hz, 1H, NCH), 6.78-6.99 (m, 3H, Ar,), 7.27-7.51 (m, 3H, Ar), 7.78 (dd, J=7.4 Hz, 1H, Ar), 10.08 (br s, 1H, NH); 13C NMR (CDCl3) δ14.66, 37.52, 49.48, 54.94, 5.91, 64.01, 64.41, 111.37, 112.12, 119.26, 122.75, 123.54, 128.04, 131.38, 131.68, 132.58, 141.44, 148.56, 149.15, 167.81, 169.47. Anal. Calcd for C21H24N2O5: C, 65.61; H, 6.29; N, 7.29. Found: C, 65.23; H, 6.52; N, 6.88.

後処理

  1. stirringThe mixture was stirred at room temperature for 2 hours
  2. temperaturewas heated
  3. temperatureto reflux for 14 hours
  4. customThe cooled reaction mixture
  5. washwas washed with hydrochloric acid (1N, 25 mL), saturated sodium bicarbonate (25 mL), brine (25 mL)
  6. dry with materialdried over sodium carbonate and sodium sulfate
  7. customRemoval of solvent in vacuo
  8. customgave a solid which
  9. filtrationThis suspension was filtered
  10. washthe solid was washed with ether (2×10 mL)

出典と根拠

ORDレコード
ord-eab829dc7ba64e7e94b0a5740d6460ef
出典データセット
uspto-grants-2003_12
特許番号
US06656964B2

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