Dichloromethane → (3aR,7R,7aR)-2-{[2-(3-dimethylaminopropoxy)phenyl]acetyl}-4,4-diphenyl-7-fluoroperhydroisoindole hydrochloride

HRID 2399991Notes

Reaction equation

HRID 2399991 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)[CH2:26][CH2:25][C@@H:24]([F:27])[C@@H:23]3[C@H:19]2[CH2:20][NH:21][CH2:22]3)[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.C(N(C(C)C)CC)(C)C.[Cl:70]CCl>>[ClH:70].[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:21]1[CH2:20][C@@H:19]2[C@@H:23]([C@H:24]([F:27])[CH2:25][CH2:26][C:18]2([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:22]1)=[O:48]

Participants

7

Reactant 6

HCID 6344Dichloromethane2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9948096(3aR,7R,7aR)-4,4-diphenyl-7-fluoroperhydroisoindoleHCID 224172542-(3-Dimethylaminopropoxy)phenylacetic acid

Product 1

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

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, 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-e13e5983a6474f6ba1ce1f91fac040c6
Source dataset
uspto-grants-1995_09
Patent number
US05451601

Reaction notes

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