Diisopropylethylamine → (3aR, 7R,7aR)-2-{{[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetyl}-4,4-diphenyl-7-fluoroperhydroisoindole

HRID 2399995ノート

反応式

HRID 2399995 の反応式
O.OC1C2N=NNC=2C=CC=1.Cl.[C:13]1([C:19]2([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:27][CH2:26][C@@H:25]([F:28])[C@@H:24]3[C@H:20]2[CH2:21][NH:22][CH2:23]3)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[N:35]1([CH2:40][CH:41]([O:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=2[CH2:50][C:51](O)=[O:52])[CH3:42])[CH2:39][CH2:38][CH2:37][CH2:36]1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>ClCCl>[N:35]1([CH2:40][CH:41]([O:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=2[CH2:50][C:51]([N:22]2[CH2:21][C@@H:20]3[C@@H:24]([C@H:25]([F:28])[CH2:26][CH2:27][C:19]3([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:23]2)=[O:52])[CH3:42])[CH2:36][CH2:37][CH2:38][CH2:39]1

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54259613{[3-(1-Pyrrolidinyl)-2-propoxy]phenyl}acetic acidHCID 67746156(3aR, 7R,7aR)-4,4-diphenyl-7-fluoroperhydroisoindole hydrochlorideHCID 178526939HCID 178526939、化合物

生成物 1

HCID 22856108(3aR, 7R,7aR)-2-{{[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetyl}-4,4-diphenyl-7-fluoroperhydroisoindole収率 41.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
20 °C

実験手順

0.04 g of hydroxybenzotriazole hydrate is added to a solution, cooled to +5° C., of 1 g of (3aR,7R,7aR)-4,4-diphenyl-7-fluoroperhydroisoindole hydrochloride and 0,924 g of 2-{[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetic acid in 40 cm3 of dry dichloromethane followed by 0.79 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.51 cm3 of diisopropylethylamine. After stirring for 2.5 hours at +5° C. and 20 hours at 20° C., the reaction mixture is washed twice with 50 cm3 of water, dried over magnesium sulphate and then concentrated to dryness at 40° C. under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 2.4 cm, height 31 cm), eluting under a nitrogen pressure of 0.5 bar with an ethyl acetate, acetic acid and water mixture (60/10/10 by volume) and collecting fractions of 25 cm3. Fractions 11 to 31 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up in 20 cm3 of dichloromethane, the solution is washed with 20 cm3 of a 1N aqueous solution of sodium hydroxide and then dried over magnesium sulphate and concentrated to dryness. This wash with a basic solution is repeated again. 0.68 g of (3aR,7R,7aR)-2-{{[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetyl}-4,4-diphenyl-7-fluoroperhydro-isoindole is obtained in the form of a white solid.

後処理

  1. washthe reaction mixture is washed twice with 50 cm3 of water
  2. dry with materialdried over magnesium sulphate
  3. concentrationconcentrated to dryness at 40° C. under reduced pressure (2.7 kPa)
  4. customThe residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 2.4 cm, height 31 cm)
  5. washeluting under a nitrogen pressure of 0.5 bar with an ethyl acetate, acetic acid and water mixture (60/10/10 by volume)
  6. customcollecting fractions of 25 cm3
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. washthe solution is washed with 20 cm3 of a 1N aqueous solution of sodium hydroxide
  9. dry with materialdried over magnesium sulphate
  10. concentrationconcentrated to dryness
  11. washThis wash with a basic solution

出典と根拠

ORDレコード
ord-e13bcb8f8538428a926cd3e89ad53af7
出典データセット
uspto-grants-1995_09
特許番号
US05451601

反応ノート

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