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

HRID 1721215Notes

Reaction equation

HRID 1721215 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.Br.[N:14]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH2:25][C:26]([OH:28])=O)[CH2:18][CH2:17][CH2:16][CH2:15]1.[ClH:29].[C:30]1([C:36]2([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C@H:44]3[C@H:40]([CH2:41][NH:42][CH2:43]3)[C@@H:39]([OH:45])[CH2:38][CH2:37]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.Cl>ClCCl.CC(C)=O.C(OCC)C.C(N(CC)CC)C>[ClH:29].[C:46]1([C:36]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C@H:44]3[C@H:40]([CH2:41][N:42]([C:26](=[O:28])[CH2:25][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[N:14]4[CH2:15][CH2:16][CH2:17][CH2:18]4)[CH2:43]3)[C@@H:39]([OH:45])[CH2:38][CH2:37]2)[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 682631,1'-CarbonyldiimidazoleHCID 22856103(3aR,4S,7aR)-7,7-diphenyl-4-perhydroisoindolol hydrochlorideHCID 67745326(2-Pyrrolidinophenyl)acetic acid hydrobromide

Product 1

HCID 22856099(3aR,4S,7aR)-7,7-diphenyl-2-[(2-pyrrolidinophenyl)acetyl]-4-perhydroisoindolol hydrochlorideYield 12.9%

Reagents, catalysts & solvents 4

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

Procedure

0.42 cm3 of triethylamine and 0.49 g of carbonyldiimidazole are added to a solution, cooled to +4° C., of 0.86 g of (2-pyrrolidinophenyl)acetic acid hydrobromide 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 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 a minimum amount of acetone and treating with a solution of hydrochloric acid in ethyl ether and 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-911b5f637376467b84294524ed1f870f
Source dataset
uspto-grants-1996_04
Patent number
US05508433

Reaction notes

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