1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (3aR*,4R*,6S*,7aS*)-4-(2-methoxyphenyl)-2-[2-(S)-(2-methoxyphenyl)propionyl]-6-methyl-4-perhydroisoindolol

HRID 55394

反応式

HRID 55394 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([OH:19])[CH2:17][CH:16]([CH3:18])[CH2:15][CH:14]2[CH:10]1[CH2:11][NH:12][CH2:13]2.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C@H:28]([CH3:32])[C:29](O)=[O:30].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C@@:9]1([OH:19])[CH2:17][C@@H:16]([CH3:18])[CH2:15][C@H:14]2[C@@H:10]1[CH2:11][N:12]([C:29](=[O:30])[C@H:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[O:21][CH3:20])[CH3:32])[CH2:13]2

参加物

7

反応物 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 11137716(S)-2-(2-Methoxyphenyl)propanoic acidHCID 19957564(3aRS,4RS,6SR,7aSR)-4-(2-methoxyphenyl)-6-methyl-4 perhydroisoindolol

生成物 1

HCID 53996359(3aR*,4R*,6S*,7aS*)-4-(2-methoxyphenyl)-2-[2-(S)-(2-methoxyphenyl)propionyl]-6-methyl-4-perhydroisoindolol収率 36.1%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

反応条件

温度
5 °C

実験手順

To a solution of 1.54 g of (3aRS,4RS,6SR,7aSR)-4-(2-methoxyphenyl)-6-methyl-4-perhydroisoindolol in 150 cm3 of dichloromethane is added 1.0 cm3 of triethylamine. The reaction is mixture is cooled to 5° C. and 1.08 g of (S)-2(2-methoxyphenyl)propionic acid, 0.10 g of 1-hydroxybenzotriazole monohydrate and 1.26 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added. The reaction mixture is maintained for 1 hour at 5° C. and for 16 hours at 20° C. and is then washed twice with 100 cm3 of water, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.060-0.200 mm, diameter 4 cm, height 70 cm), eluting under a pressure of 0.7 bar with a mixture of ethyl acetate and cyclohexane [by volume: 20/80 (2 dm3) then 30/70 (2 dm3) then 40/60 (2 dm3) and collecting 60 cm3 fractions. Fractions 57 to 72 are concentrated and, after drying at 40° C. at 15 Pa, 0.90 g of (3aR*,4R*,6S*,7aS*)-4-(2-methoxyphenyl)-2-[2-(S)-(2-methoxyphenyl)propionyl]-6-methyl-4-perhydroisoindolol is obtained in the form of a white solid.

後処理

  1. temperatureThe reaction mixture is maintained for 1 hour at 5° C. and for 16 hours at 20° C.
  2. washis then washed twice with 100 cm3 of water
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a column of silica gel (0.060-0.200 mm, diameter 4 cm, height 70 cm)
  7. washeluting under a pressure of 0.7 bar with a mixture of ethyl acetate and cyclohexane [by volume
  8. custom20/80 (2 dm3) then 30/70 (2 dm3) then 40/60 (2 dm3) and collecting 60 cm3 fractions
  9. concentrationFractions 57 to 72 are concentrated
  10. customafter drying at 40° C. at 15 Pa

出典と根拠

ORDレコード
ord-3387721eaebe4b7397befe85fe6d9751
出典データセット
uspto-grants-1997_04
特許番号
US05624950

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