Water → [2-(2,6-Dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamic acid tert-butyl ester

HRID 9950

反応式

HRID 9950 の反応式
CO[C:3](=[O:23])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:5]=1[C:19]([O:21]C)=O.Cl.[NH2:25][CH:26]1[CH2:32][CH2:31][C:30](=[O:33])[NH:29][C:27]1=[O:28].O>CN(C=O)C>[C:15]([O:14][C:12](=[O:13])[NH:11][CH2:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:4]2[C:5]=1[C:19](=[O:21])[N:25]([CH:26]1[CH2:32][CH2:31][C:30](=[O:33])[NH:29][C:27]1=[O:28])[C:3]2=[O:23])([CH3:16])([CH3:17])[CH3:18]

参加物

5

反応物 3

HCID 962WaterHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 21988573Methyl-3-[(t-butoxycarbonylamino)methyl]-2-(methoxycarbonyl)benzoate

生成物 1

HCID 9908253[2-(2,6-Dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

Diusopropylethylamine (3.20 g, 25 mmol) was added to a stirred suspension of methyl-3-[(t-butoxycarbonylamino)methyl]-2-(methoxycarbonyl)benzoate (8.00 g, 25 mmol) and aminoglutarimide hydrochloride (4.07 g, 25 mmol) in DMF (60 ml). The mixture was heated to 120° C. for 24 hours and then cooled to room temperature. The mixture was poured into cold water (300 ml) and extracted with ethyl acetate (4×100 ml each). The combined ethyl acetate extracts were washed with water (2×50 ml), brine (50 ml) and dried. Solvent was removed in vacuo and the product purified by flash chromatography (dichloromethane/ethyl acetate 8 to 2) to yield 4.66 g of recovered starting material and 3.31 g (82%) of the product as a white solid: mp 180–182° C.; 1H NMR (CDCl3) δ 8.51 (s, 1H), 7.81–7.67 (m, 3H), 5.54 (b, 1H), 5.03–4.96 (dd, J=5.2 and 11.2 Hz, 1H), 4.66 (d, J=6.3 Hz, 2H), 2.95–2.74 (m, 3H), 2.18–2.14 (m, 1H), 1.43 (s, 9H); 13C NMR (CDCl3) δ 170.99, 168.08, 167.95, 167.07, 155.86, 139.17, 135.00, 134.61, 132.15, 128.22, 122.82, 79.81, 49.21, 40.53, 31.33, 28.32, 22.58; Anal. Calcd for C19H21N3O6: C, 58.91; H, 5.46; N, 10.85. Found: C, 59.08; H, 5.51; N, 10.69.

後処理

  1. temperaturecooled to room temperature
  2. extractionextracted with ethyl acetate (4×100 ml each)
  3. washThe combined ethyl acetate extracts were washed with water (2×50 ml), brine (50 ml)
  4. customdried
  5. customSolvent was removed in vacuo
  6. customthe product purified by flash chromatography (dichloromethane/ethyl acetate 8 to 2)
  7. customto yield 4.66 g
  8. customof recovered

出典と根拠

ORDレコード
ord-bae69bccc992457a8d4c901678105e5d
出典データセット
uspto-grants-2006_08
特許番号
US07091353B2

関連ノート

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