Indole-3-Acetic Acid → (3aRS,4RS,7aRS)-7,7-diphenyl-2-(3-indolylacetyl)-4-(2-methoxyphenyl)-perhydroisoindol-4-ol

HRID 2211420Notes

Reaction equation

HRID 2211420 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[NH:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH2:22][C:23]([OH:25])=O)=[CH:14]1.Cl.[C:27]1([C:33]2([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH:41]3[CH:37]([CH2:38][NH:39][CH2:40]3)[C:36]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=3[O:49][CH3:50])([OH:42])[CH2:35][CH2:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)CC)C>C(Cl)Cl>[C:51]1([C:33]2([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:41]3[CH:37]([CH2:38][N:39]([C:23](=[O:25])[CH2:22][C:15]4[C:16]5[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=5)[NH:13][CH:14]=4)[CH2:40]3)[C:36]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=3[O:49][CH3:50])([OH:42])[CH2:35][CH2:34]2)[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1

Participants

6

Reactant 4

HCID 802Indole-3-Acetic AcidHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 21264542(3aRS,4RS,7aRS)-7,7-diphenyl-4-(2-methoxyphenyl)-perhydroisoindol-4-ol hydrochloride

Product 1

HCID 18994349(3aRS,4RS,7aRS)-7,7-diphenyl-2-(3-indolylacetyl)-4-(2-methoxyphenyl)-perhydroisoindol-4-olYield 12.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

0.41 g of carbonyldiimidazole is added to a solution of 0.44 g of 3-indolylacetic acid in 20 cm3 of dry methylene chloride. The mixture is stirred at room temperature for 1 hour and a suspension of 1.1 g of (3aRS,4RS,7aRS)-7,7-diphenyl-4-(2-methoxyphenyl)-perhydroisoindol-4-ol hydrochloride in 25 cm3 of dry methylene chloride and then 0.7 cm3 of triethylamine are subsequently added in succession. The reaction mixture is stirred at room temperature for 24 hours, diluted with 100 cm3 of methylene chloride, washed with 100 cm3 of water (twice) and then with 100 cm3 of an aqueous saturated solution of sodium chloride, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed over a Merck silica gel column (particle size 0.04-0.06 mm, diameter 2 cm, height 22 cm) by eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (35/65 by volume) and collecting fractions of 20 cm3. Fractions 7 to 8 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). The residue is triturated in diisopropyl ether. 0.17 g of (3aRS,4RS,7aRS)-7,7-diphenyl-2-(3-indolylacetyl)-4-(2-methoxyphenyl)-perhydroisoindol-4-ol is obtained in the form of a white solid.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 24 hours
  2. washwashed with 100 cm3 of water (twice) and then with 100 cm3 of an aqueous saturated solution of sodium chloride
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe residue is chromatographed over a Merck silica gel column (particle size 0.04-0.06 mm, diameter 2 cm, height 22 cm)
  6. washby eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (35/65 by volume)
  7. customcollecting fractions of 20 cm3
  8. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe residue is triturated in diisopropyl ether

Sources & evidence

ORD record
ord-dc0fb8f70e2849b19f76b9716b733741
Source dataset
uspto-grants-1995_10
Patent number
US05463077

Reaction notes

Loading…