1,1'-Carbonyldiimidazole → (3aR, 7R,7aR)-4,4-diphenyl-7-fluoro-2-[(2-pyrrolidinophenyl)acetyl]perhydroisoindole

HRID 1721207ノート

反応式

HRID 1721207 の反応式
C(N1C=CN=C1)(N1C=CN=C1)=O.Br.[N:14]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH2:25][C:26]([OH:28])=O)[CH2:18][CH2:17][CH2:16][CH2:15]1.Cl.[C:30]1([C:36]2([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH2:44][CH2:43][C@@H:42]([F:45])[C@@H:41]3[C@H:37]2[CH2:38][NH:39][CH2:40]3)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>ClCCl.C(N(CC)CC)C>[C:46]1([C:36]2([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:44][CH2:43][C@@H:42]([F:45])[C@@H:41]3[C@H:37]2[CH2:38][N:39]([C:26](=[O:28])[CH2:25][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:14]2[CH2:15][CH2:16][CH2:17][CH2:18]2)[CH2:40]3)[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

参加物

6

反応物 3

HCID 682631,1'-CarbonyldiimidazoleHCID 67745326(2-Pyrrolidinophenyl)acetic acid hydrobromideHCID 67746156(3aR, 7R,7aR)-4,4-diphenyl-7-fluoroperhydroisoindole hydrochloride

生成物 1

HCID 53829412(3aR, 7R,7aR)-4,4-diphenyl-7-fluoro-2-[(2-pyrrolidinophenyl)acetyl]perhydroisoindole収率 16.6%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒3 回HCID 8471Triethylamine溶媒2 回

実験手順

0.28 cm3 of triethylamine and 0.32 g of carbonyldiimidazole are added to a solution, cooled to 4° C., of 0.57 g of (2-pyrrolidinophenyl)acetic acid hydrobromide 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 24 hours and then diluted with 100 cm3 of dichloromethane, washed twice 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 3.5 cm, height 38 cm), eluting under a nitrogen pressure of 0.5 bar with a cyclohexane and ethyl acetate mixture (70/30 by volume) and collecting fractions of 20 cm3. Fractions 26 to 54 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from an acetonitrile and diisopropyl oxide mixture (25/75 by volume). 0.16 g of (3aR, 7R,7aR)-4,4-diphenyl-7-fluoro-2-[(2-pyrrolidinophenyl)acetyl]perhydroisoindole is obtained in the form of white crystals; melting point 170° C.

後処理

  1. stirringThe reaction mixture is stirred at room temperature for 24 hours
  2. washwashed twice 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 3.5 cm, height 38 cm)
  7. washeluting under a nitrogen pressure of 0.5 bar with a cyclohexane and ethyl acetate mixture (70/30 by volume)
  8. customcollecting fractions of 20 cm3
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  10. customThe residue is crystallized from an acetonitrile and diisopropyl oxide mixture (25/75 by volume)

出典と根拠

ORDレコード
ord-5c7d62b8d742489bb3b6f731e0c1a843
出典データセット
uspto-grants-1996_04
特許番号
US05508433

反応ノート

読み込み中…