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

HRID 1721204Notes

Reaction equation

HRID 1721204 reaction equation
CN(C)CCCN=C=NCC.[ClH:12].[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.[CH3:35][N:36]([CH3:51])[CH2:37][CH2:38][CH2:39][O:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[CH2:47][C:48](O)=[O:49].ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>ClCCl>[ClH:12].[CH3:51][N:36]([CH3:35])[CH2:37][CH2:38][CH2:39][O:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[CH2:47][C:48]([N:22]1[CH2:21][C@@H:20]2[C@@H:24]([C@H:25]([F:28])[CH2:26][CH2:27][C:19]2([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:23]1)=[O:49]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 224172542-(3-Dimethylaminopropoxy)phenylacetic acidHCID 67746156(3aR, 7R,7aR)-4,4-diphenyl-7-fluoroperhydroisoindole hydrochloride

Product 1

HCID 67809527(3aR,7R,7aR)-2-{[2-(3-dimethylaminopropoxy)phenyl]acetyl}-4,4-diphenyl-7-fluoroperhydroisoindole hydrochlorideYield 73.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 0.5 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide in 50 cm3 of dry dichloromethane is added over 10 minutes to a solution, cooled to +4° C., of 0.72 g of (3aR, 7R,7aR)-4,4-diphenyl-7-fluoroperhydroisoindole hydrochloride, 0.5 g of 2-(3-dimethylaminopropoxy)phenylacetic acid, 0.03 g of 1-hydroxybenzotriazole in 75 cm3 of dichloromethane, followed by 0.37 cm3 of diisopropylethylamine. The reaction mixture is stirred for 3 hours at 0° C. and then washed twice with 50 cm3 of water and twice 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 taken up in 21 cm3 of 0.1N hydrochloric acid, 50 cm3 of diethyl ether and 30 cm3 of water. The aqueous phase is separated and freeze-dried to give 0.85 g of (3aR, 7R,7aR)-2-([2-(3-dimethylaminopropoxy)phenyl]acetyl)-4,4-diphenyl-7-fluoroperhydroisoindole hydrochloride in the form of a white freeze-dried product.

Workup

  1. washwashed twice with 50 cm3 of water and twice 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 aqueous phase is separated
  5. customfreeze-dried

Sources & evidence

ORD record
ord-c860b48c8d8a419e85e19b6964c7f5eb
Source dataset
uspto-grants-1996_04
Patent number
US05508433

Reaction notes

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