(3-Bromopropyl)benzene → (1R,3R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-methyl-1-(3-phenyl-propyl)-piperidinium bromide

HRID 551384Notes

Reaction equation

HRID 551384 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([O:8][C:9](=[O:22])[C:10]([OH:21])([C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)[CH2:3]1.[Br:23][CH2:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(#N)C>[Br-:23].[OH:21][C:10]([C:11]1[S:12][CH:13]=[CH:14][CH:15]=1)([C:16]1[S:17][CH:18]=[CH:19][CH:20]=1)[C:9]([O:8][C@@H:4]1[CH2:5][CH2:6][CH2:7][N@@+:2]([CH3:1])([CH2:24][CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:3]1)=[O:22]

Participants

4

Reactant 2

HCID 12503(3-Bromopropyl)benzeneHCID 67199874Hydroxy-di-thiophen-2-yl-acetic acid (R)-1-methyl-piperidin-3-yl ester

Product 1

HCID 11191882(1R,3R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-methyl-1-(3-phenyl-propyl)-piperidinium bromide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

Hydroxy-di-thiophen-2-yl-acetic acid (R)-1-methyl-piperidin-3-yl ester (2.1 g, 0.00623 mol) is dissolved in acetonitrile (5 ml) at 60° C. and 1-bromo-3-phenylpropane (1.43 ml, 0.00934 mol) is added dropwise. After 18 hours stirring at 60° C., the white solid is broken up and stirring continued for another 8 hours at this temperature. The suspension is cooled to room temperature and the solid filtered off. The solid is recrystallised from 3 ml of acetonitrile containing 2 drops of water to yield (1R,3R)-3-(2-Hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-methyl-1-(3-phenyl-propyl)-piperidinium bromide (96a) as a white solid. The reaction mixture mother liquid is evaporated to dryness and the residue is purified by flash chromatography over C18 silica gel (70 g) using a gradient of water/acetonitrile 10010 to 0/100 over 25 minutes at 20 ml/min. The product containing fractions are combined and evaporated to dryness to yield (1S,3R)-3-(2-hydroxy-2,2-di-thiophen-2-yl-acetoxy)-1-methyl-1-(3-phenyl-propyl)-piperidinium bromide (96b) as a white amorphous solid.

Workup

  1. stirringstirring
  2. waitcontinued for another 8 hours at this temperature
  3. temperatureThe suspension is cooled to room temperature
  4. filtrationthe solid filtered off
  5. customThe solid is recrystallised from 3 ml of acetonitrile containing 2 drops of water

Sources & evidence

ORD record
ord-faa204aa7bbb4f97871fa5323933ede0
Source dataset
uspto-grants-2011_05
Patent number
US07947730B2

Reaction notes

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