Sodium Carbonate → 3-Cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionic acid methyl ester

HRID 1935205Notes

Reaction equation

HRID 1935205 reaction equation
[CH3:1][O:2][C:3](=[O:18])[CH:4]([C:11]1[CH:16]=[CH:15][C:14](I)=[CH:13][CH:12]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[N:19]1[CH:24]=[CH:23][CH:22]=[C:21](B(O)O)[CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:18])[CH:4]([C:11]1[CH:16]=[CH:15][C:14]([C:21]2[CH:20]=[N:19][CH:24]=[CH:23][CH:22]=2)=[CH:13][CH:12]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 674834473-Cyclopentyl-2-(4-iodo-phenyl)-propionic acid methyl ester

Product 1

HCID 674834933-Cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionic acid methyl esterYield 92.7%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
25 °C

Procedure

A slurry of dichlorobis(triphenylphosphine)palladium(II) (119 mg, 0.17 mmol) in 1,2-dimethoxyethane (10 mL) was treated with 3-cyclopentyl-2-(4-iodo-phenyl)-propionic acid methyl ester (1.00 g, 2.79 mmol). The reaction slurry was stirred at 25° C. for 10 min and then treated with a solution of pyridine-3-boronic acid (515 mg, 4.19 mmol) and a 2M aqueous sodium carbonate solution (2.8 mL, 5.58 mmol) in water (5 mL). The resulting reaction mixture was heated under reflux for 90 min. The reaction mixture was allowed to cool to 25° C. and then filtered to remove the catalyst. The filtrate was partitioned between water and methylene chloride, and the layers were separated. The aqueous layer was further extracted with methylene chloride (75 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionic acid methyl ester (800 mg, 92%) as a brown oil: EI-HRMS m/e calcd for C20H23NO2 (M+) 309.1729, found 309.1728.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureunder reflux for 90 min
  4. temperatureto cool to 25° C.
  5. filtrationfiltered
  6. customto remove the catalyst
  7. customThe filtrate was partitioned between water and methylene chloride
  8. customthe layers were separated
  9. extractionThe aqueous layer was further extracted with methylene chloride (75 mL)
  10. dry with materialThe combined organic extracts were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1bb03eca181f42118887362a3bae10b4
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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