Acetonitrile → (1r/s,3r)-3-(2-Hydroxy-2,2-diphenyl-acetoxy)-1-methyl-1-(2-phenoxy-propyl)-piperidinium bromide

HRID 551383Notes

Reaction equation

HRID 551383 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([O:8][C:9](=[O:24])[C:10]([OH:23])([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:3]1.[Br:25]C[CH2:27][CH2:28][O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[C:36](#N)C>>[Br-:25].[OH:23][C:10]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:9]([O:8][C@@H:4]1[CH2:5][CH2:6][CH2:7][N+:2]([CH3:36])([CH2:1][CH:28]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH3:27])[CH2:3]1)=[O:24]

Participants

4

Reactant 3

HCID 6342AcetonitrileHCID 68522Benzene, (3-bromopropoxy)-HCID 10616048Hydroxy-diphenyl-acetic acid (R)-1-methyl-piperidin-3-yl ester

Product 1

HCID 131728894(1r/s,3r)-3-(2-Hydroxy-2,2-diphenyl-acetoxy)-1-methyl-1-(2-phenoxy-propyl)-piperidinium bromide

Conditions

Temperature
60 °C

Procedure

Hydroxy-diphenyl-acetic acid (R)-methyl-piperidin-3-yl ester (1.7 g, 0.00523 mol) and (3-bromo-propoxy)-benzene (1.2 ml, 0.00781 mol) are dissolved in acetonitrile (2 ml) and stirred at 60° C. over night. The reaction mixture is cooled to room temperature and evaporated to dryness. The residue is taken up in DCM and extracted with water. The aqueous layer is washed with DCM (3×20 ml) and evaporated to dryness. The residue is purified by flash chromatography over C18 silica gel (70 g) using a gradient of water/acetonitrile 100/0 to 0/100 over 25 minutes at 20 ml/min. The product containing fractions were combined and evaporated to yield 700 mg of the title compound as a white foam.

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. customevaporated to dryness
  3. extractionextracted with water
  4. washThe aqueous layer is washed with DCM (3×20 ml)
  5. customevaporated to dryness
  6. customThe residue is purified by flash chromatography over C18 silica gel (70 g)
  7. customover 25 minutes
  8. additionThe product containing fractions
  9. customevaporated

Sources & evidence

ORD record
ord-37ee256d68654e59bb8f1970630f586e
Source dataset
uspto-grants-2011_05
Patent number
US07947730B2

Reaction notes

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