1,1'-Carbonyldiimidazole → (3aR,7R,7aR)-4,4-diphenyl-7-fluoro-2-[(S)-2-(2-methoxyphenyl)propionyl]perhydroisoindole

HRID 1721210ノート

反応式

HRID 1721210 の反応式
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C@H:21]([CH3:25])[C:22]([OH:24])=O.Cl.[C:27]1([C:33]2([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:41][CH2:40][C@@H:39]([F:42])[C@@H:38]3[C@H:34]2[CH2:35][NH:36][CH2:37]3)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>ClCCl.C(N(CC)CC)C>[C:43]1([C:33]2([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:41][CH2:40][C@@H:39]([F:42])[C@@H:38]3[C@H:34]2[CH2:35][N:36]([C:22](=[O:24])[C@H:21]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][CH3:13])[CH3:25])[CH2:37]3)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

参加物

6

反応物 3

HCID 682631,1'-CarbonyldiimidazoleHCID 11137716(S)-2-(2-Methoxyphenyl)propanoic acidHCID 67746156(3aR, 7R,7aR)-4,4-diphenyl-7-fluoroperhydroisoindole hydrochloride

生成物 1

HCID 54246184(3aR,7R,7aR)-4,4-diphenyl-7-fluoro-2-[(S)-2-(2-methoxyphenyl)propionyl]perhydroisoindole収率 20.8%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒3 回HCID 8471Triethylamine溶媒

実験手順

0.32 g of carbonyldiimidazole is added to a solution, cooled to +4° C., of 0.36 g of (S)-2-(2-methoxyphenyl)propionic acid in 20 cm3 of dry dichloromethane. The mixture is stirred for one hour at +4° C. and then a solution of 0.67 g of (3aR, 7R,7aR)-4,4-diphenyl- 7-fluoroperhydroisoindole hydrochloride in 20 cm3 of dry dichloromethane and 0.28 cm3 of triethylamine is added. The reaction mixture is stirred at room temperature for 20 hours, diluted with 200 cm3 of dichloromethane and then washed with 50 cm3 of water, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 20 cm), eluting under a nitrogen pressure of 0.4 bar with an ethyl acetate and cyclohexane mixture (60/40 by volume) and collecting fractions of 20 cm3. Fractions 10 to 15 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from 0.6 cm3 of isopropyl oxide. The crystals obtained are drained, washed with isopropyl oxide, and then dried. 0.19 g of (3aR, 7R,7aR)-4,4-diphenyl-7-fluoro-2-[ (S)-2-(2methoxyphenyl)propionyl]perhydroisoindole is obtained in the form of white crystals; melting point 195° C.

後処理

  1. stirringThe reaction mixture is stirred at room temperature for 20 hours
  2. washwashed with 50 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 silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 20 cm)
  7. washeluting under a nitrogen pressure of 0.4 bar with an ethyl acetate and cyclohexane mixture (60/40 by volume)
  8. customcollecting fractions of 20 cm3
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  10. customThe residue is crystallized from 0.6 cm3 of isopropyl oxide
  11. customThe crystals obtained
  12. washwashed with isopropyl oxide
  13. customdried

出典と根拠

ORDレコード
ord-af56c69773794f9d9e2350957362f0fd
出典データセット
uspto-grants-1996_04
特許番号
US05508433

反応ノート

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