Hydrochloric Acid → (3aR,4S,7aR)-7,7-diphenyl-2-[(2-pyrrolidinophenyl)acetyl]-4-perhydroisoindolol hydrochloride

HRID 2400013Notes

Reaction equation

HRID 2400013 reaction equation
C(C1NC=CN=1)(C1NC=CN=1)=O.[N:13]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH2:24][C:25]([OH:27])=O)[CH2:17][CH2:16][CH2:15][CH2:14]1.[ClH:28].[C:29]1([C:35]2([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C@H:43]3[C@H:39]([CH2:40][NH:41][CH2:42]3)[C@@H:38]([OH:44])[CH2:37][CH2:36]2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.Cl>ClCCl.CC(C)=O.C(OCC)C.C(N(CC)CC)C>[ClH:28].[C:45]1([C:35]2([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C@H:43]3[C@H:39]([CH2:40][N:41]([C:25](=[O:27])[CH2:24][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[N:13]4[CH2:14][CH2:15][CH2:16][CH2:17]4)[CH2:42]3)[C@@H:38]([OH:44])[CH2:37][CH2:36]2)[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 22856103(3aR,4S,7aR)-7,7-diphenyl-4-perhydroisoindolol hydrochlorideHCID 230093992-[2-(Pyrrolidin-1-yl)phenyl]acetic acid

Product 1

HCID 22856099(3aR,4S,7aR)-7,7-diphenyl-2-[(2-pyrrolidinophenyl)acetyl]-4-perhydroisoindolol hydrochloride

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent2×

Conditions

Temperature
4 °C

Procedure

0.42 cm3 of triethylamine and 0.49 g of carbonyl-diimidazole are added to a solution, cooled to +4° C., of 0.86 g of the hydrobromide salt of (2-pyrrolidinophenyl)acetic acid in 20 cm3 of dry dichloromethane. The mixture is stirred for one hour at 4° C. and then a solution of 1 g of (3aR,4S,7aR)-7,7-diphenyl-4-perhydroisoindolol hydrochloride and 0.42 cm3 of triethylamine in 10 cm3 of dry dichloromethane, is added. The reaction mixture is stirred at room temperature for 24 hours, and then washed twice with 10 cm3 of water and then with an aqueous solution of sodium hydrogen carbonate, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The product, which is obtained in the form of a base, is converted to the hydrochloride by dissolving in the minimum amount of acetone, by treating with a solution of hydrochloric acid in ethyl ether, and by adding ethyl ether. The solid obtained is triturated in ethyl ether and then dried. 0.2 g of (3aR,4S,7aR)-7,7-diphenyl-2-[(2-pyrrolidinophenyl)acetyl]-4-perhydroisoindolol hydrochloride is obtained in the form of a beige solid.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 24 hours
  2. washwashed twice with 10 cm3 of water
  3. dry with materialwith an aqueous solution of sodium hydrogen carbonate, dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe product, which is obtained in the form of a base
  7. customThe solid obtained
  8. customis triturated in ethyl ether
  9. customdried

Sources & evidence

ORD record
ord-ac23753ac09547fd9e9baf148e6bdcfa
Source dataset
uspto-grants-1995_09
Patent number
US05451601

Reaction notes

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