Potassium Iodide → 4-{4-[3-((R)-2-Methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-4-oxo-2-pyridin-2-yl-butyric acid ethyl ester

HRID 2042638Notes

Reaction equation

HRID 2042638 reaction equation
[CH2:1]([O:3][C:4](=[O:26])[CH:5]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1)[CH2:6][C:7]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH2:18]Cl)=[CH:11][CH:10]=1)=[O:8])[CH3:2].[CH3:27][C@@H:28]1[CH2:32][CH2:31][CH2:30][NH2+:29]1.C1(S([O-])(=O)=O)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C>[CH2:1]([O:3][C:4](=[O:26])[CH:5]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1)[CH2:6][C:7]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH2:18][N:29]2[CH2:30][CH2:31][CH2:32][C@H:28]2[CH3:27])=[CH:11][CH:10]=1)=[O:8])[CH3:2]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 596520644-[4-(3-Chloro-propoxy)-phenyl]-4-oxo-2-pyridin-2-yl-butyric acid ethyl esterHCID 86646919(R)-2-methylpyrrolidine benzene sulfonate

Product 1

HCID 596518864-{4-[3-((R)-2-Methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-4-oxo-2-pyridin-2-yl-butyric acid ethyl esterYield 30.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a 100 mL round bottom flask, 4-[4-(3-chloro-propoxy)-phenyl]-4-oxo-2-pyridin-2-yl-butyric acid ethyl ester (2.77 g, 7.4 mmol), benzenesulfonate (R)-2-methyl-pyrrolidinium (3.59 g, 14.7 mmol), potassium carbonate (4.07 g, 29.5 mmol), and potassium iodide (100 mg, 0.6 mmol) in acetonitrile (100 mL) was heated to reflux 14 h. The reaction was cooled and the solvent concentrated under vacuum. The slurry was partitioned between methylene chloride and water, and then washed with water 3 times. The organics were chromatographed through silica gel with methylene chloride/methanol (95:5) eluent. Ethereal HCl was added to make the bis HCl salt and produce 960 mg (28%) of an amorphous solid. MS m/z 425 (M+H).

Workup

  1. temperatureto reflux 14 h
  2. temperatureThe reaction was cooled
  3. concentrationthe solvent concentrated under vacuum
  4. customThe slurry was partitioned between methylene chloride and water
  5. washwashed with water 3 times
  6. customThe organics were chromatographed through silica gel with methylene chloride/methanol (95:5) eluent
  7. additionEthereal HCl was added

Sources & evidence

ORD record
ord-956afd2de90346ae9788aa1d4b6e7729
Source dataset
uspto-grants-2013_11
Patent number
US08586588B2

Reaction notes

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