3-Aminopiperidine-2,6-dione hydrochloride → [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-methyl-carbamic acid t-butyl ester

HRID 240671ノート

反応式

HRID 240671 の反応式
[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:13]([C:14]([OH:16])=O)[C:12]=1[C:20]([OH:22])=O)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:24][CH:25]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:26]1=[O:27]>N1C=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[C:13]2[C:12]=1[C:20](=[O:22])[N:24]([CH:25]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:26]1=[O:27])[C:14]2=[O:16])[CH3:9])([CH3:2])([CH3:3])[CH3:4]

参加物

4

反応物 2

HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 670196793-[(t-Butoxycarbonyl-methyl-amino)-methyl]phthalic acid

生成物 1

HCID 24755597[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-methyl-carbamic acid t-butyl ester収率 60%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

実験手順

A stirred mixture of 3-[(t-butoxycarbonyl-methyl-amino)-methyl]-phthalic acid (2.3 g, 7.1 mmol) from above and α-aminoglutarimide hydrochloride (1.3 g, 7.8 mmol) in pyridine (40 mL) was refluxed for 5 hours. The mixture was cooled and concentrated in vacuo. The residue was dissolved in EtOAc (100 mL) and water (50 mL). The EtOAc solution was separated and washed with water (40 mL), IN citric acid (2×40 mL), water (2×40 mL), and brine (40 mL), and then dried (MgSO4). Solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, CH2Cl2: EtOAc 8:2) to give [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-methyl-carbamic acid t-butyl ester (1.7 g, 60%): mp 138-140° C.; 1H NMR (DMSO-d6) δ 11.14 (s, 1H), 7.91-7.81 (m, 2H), 7.57 (b, 1H), 5.19-5.12 (dd, J=5.3 and 12.6 Hz, 1H), 4.85 (s, 2H), 2.97-2.83 (m, 1H), 2.89 (s, 3H), 2.63-2.50 (m, 2H), 2.07-2.03 (m, 1H), 1.44-1.29 (d, 9H); 13CNMR (DMSO-d6) δ 172.70, 169.74, 167.48, 166.87, 154.75, 138.31, 134.99, 132.31, 131.74, 127.42, 121.98, 79.13, 48.86, 47.32, 34.84, 30.90, 27.93, 21.94; Anal. Calcd. for C20H23N3O6: C, 59.84; H, 5.78; N, 10.47. Found: C, 59.51; H, 5.68; N, 10.31.

後処理

  1. temperaturewas refluxed for 5 hours
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc (100 mL)
  5. customThe EtOAc solution was separated
  6. washwashed with water (40 mL), IN citric acid (2×40 mL)
  7. dry with materialwater (2×40 mL), and brine (40 mL), and then dried (MgSO4)
  8. customSolvent was removed in vacuo
  9. customthe residue was purified by flash chromatography (SiO2, CH2Cl2: EtOAc 8:2)

出典と根拠

ORDレコード
ord-01403058b3864d85bfd79a45f2402b4e
出典データセット
uspto-grants-2014_02
特許番号
US08648096B2

反応ノート

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