1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (3aR,4S,7aR)-2-{[2-(3-dimethylaminopropoxy)phenyl]-acetyl}-7,7-diphenyl-4-perhydroisoindolol

HRID 2400016Notes

Reaction equation

HRID 2400016 reaction equation
CN(C)CCCN=C=NCC.[C:12]1([C:18]2([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C@H:26]3[C@H:22]([CH2:23][NH:24][CH2:25]3)[C@@H:21]([OH:27])[CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH3:34][N:35]([CH3:50])[CH2:36][CH2:37][CH2:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[CH2:46][C:47](O)=[O:48].ON1C2C=CC=CC=2N=N1>ClCCl>[CH3:50][N:35]([CH3:34])[CH2:36][CH2:37][CH2:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[CH2:46][C:47]([N:24]1[CH2:23][C@H:22]2[C@H:26]([C:18]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:19][CH2:20][C@@H:21]2[OH:27])[CH2:25]1)=[O:48]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 224172542-(3-Dimethylaminopropoxy)phenylacetic acidHCID 22856102(3aR,4S,7aR)-7,7-diphenyl-4-perhydroisoindolol

Product 1

HCID 22856095(3aR,4S,7aR)-2-{[2-(3-dimethylaminopropoxy)phenyl]-acetyl}-7,7-diphenyl-4-perhydroisoindololYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

0,766 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide is added to a solution, cooled to 10° C., of 1 g of (3aR,4S,7aR)-7,7-diphenyl-4-perhydroisoindolol, 0.97 g of 2-(3-dimethylaminopropoxy)phenylacetic acid and 0.05 g of 1-hydroxybenzotriazole in 50 cm3 of dichloromethane. The reaction mixture is stirred for 90 minutes 20° C. and then washed twice with 50 cm3 of water and with 50 cm3 of a saturated solution of sodium chloride. The organic phase is dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (particle size 0.2-0.063 mm, diameter 2.9 cm, height 23 cm), eluting under a nitrogen pressure of 0.7 bar with 1,2-dichloroethane and methanol mixtures (1 liter at 90/10 by volume and 1.5 liters at 70/30 by volume) and collecting fractions of 25 cm3. Fractions 10 to 84 are pooled and concentrated to dryness under reduced pressure (2.7 kPa) to give 1.1 g of (3aR,4S,7aR)-2-{[2-(3-dimethylaminopropoxy)phenyl]-acetyl}-7,7-diphenyl-4-perhydroisoindolol in the form of a cream-colored meringue.

Workup

  1. washwashed twice with 50 cm3 of water and with 50 cm3 of a saturated solution of sodium chloride
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  4. customThe residue is chromatographed on a silica gel column (particle size 0.2-0.063 mm, diameter 2.9 cm, height 23 cm)
  5. washeluting under a nitrogen pressure of 0.7 bar with 1,2-dichloroethane and methanol mixtures (1 liter at 90/10 by volume and 1.5 liters at 70/30 by volume)
  6. customcollecting fractions of 25 cm3
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-f3416806485b4988aabf07c04c37e073
Source dataset
uspto-grants-1995_09
Patent number
US05451601

Reaction notes

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