1,4-Dioxane hydrochloride → 3,5-difluoro-4-[(3S,4S)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]benzoic acid hydrochloride

HRID 732696Notes

Reaction equation

HRID 732696 reaction equation
C(OC([N:8]([CH2:21][C@@H:22]1[C@@H:26]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:25][N:24]([C:33]2[C:41]([F:42])=[CH:40][C:36]([C:37]([OH:39])=[O:38])=[CH:35][C:34]=2[F:43])[CH2:23]1)[C@@H:9]([C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:10])=O)(C)(C)C.[ClH:44].O1CCOCC1>O1CCOCC1>[ClH:44].[F:42][C:41]1[CH:40]=[C:36]([CH:35]=[C:34]([F:43])[C:33]=1[N:24]1[CH2:25][C@H:26]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C@@H:22]([CH2:21][NH:8][C@@H:9]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=[CH:13][CH:12]=2)[CH3:10])[CH2:23]1)[C:37]([OH:39])=[O:38]

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 689144544-[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]-3,5-difluorobenzoic acid

Product 1

HCID 689166923,5-difluoro-4-[(3S,4S)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]benzoic acid hydrochloride

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A 20 ml 1,4-dioxane solution of 2.01 g of 4-[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]-3,5-difluorobenzoic acid was mixed with 2.0 ml of 4 M hydrogen chloride/1,4-dioxane and stirred overnight at room temperature. The reaction solution was concentrated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol). The purified product was dissolved in 1,4-dioxane-diethyl ether, 4 M hydrogen chloride/1,4-dioxane was added thereto, and the thus precipitated crystals were collected by filtration and then recrystallized from 1,4-dioxane-water, thereby obtaining 484 mg of 3,5-difluoro-4-[(3S,4S)-3-({[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]benzoic acid hydrochloride.

Workup

  1. concentrationThe reaction solution was concentrated under a reduced pressure
  2. customthe thus obtained residue was purified by a silica gel column chromatography (chloroform-methanol)
  3. dissolutionThe purified product was dissolved in 1,4-dioxane-diethyl ether
  4. addition4 M hydrogen chloride/1,4-dioxane was added
  5. filtrationthe thus precipitated crystals were collected by filtration
  6. customrecrystallized from 1,4-dioxane-water

Sources & evidence

ORD record
ord-1971a4a5a2154192a0a191a263b3224d
Source dataset
uspto-grants-2009_09
Patent number
US07585886B2

Reaction notes

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