D-Proline → HCID 66652985, compound

HRID 1524270Notes

Reaction equation

HRID 1524270 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].C(=O)([O-])[O-].[K+].[K+].[NH:19]1[CH2:26][CH2:25][CH2:24][C@@H:20]1[C:21]([OH:23])=[O:22]>CN(C)C(=O)C.O.[Cu]I>[CH2:8]([O:7][C:5]([C:4]1[CH:3]=[C:2]([N:19]2[CH2:26][CH2:25][CH2:24][C@@H:20]2[C:21]([OH:23])=[O:22])[CH:12]=[CH:11][CH:10]=1)=[O:6])[CH3:9]

Participants

7

Reactant 3

HCID 8988D-ProlineHCID 11430Potassium CarbonateHCID 143542Ethyl 3-iodobenzoate

Product 1

HCID 66652985HCID 66652985, compoundYield 19.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

Add ethyl 3-iodobenzoate (1.5 mL, 8.9 mmol), potassium carbonate (1.3 g, 9.4 mmol) and copper (I) iodide (0.17 g, 0.89 mmol) to a solution of D-proline (1.00 g, 8.69 mmol) in N,N-dimethylacetamide (20 mL). Bubble Argon through the mixture for 30 min then heat the reaction to 90° C. for 15 hours. Cool the mixture to room temperature, dilute with water, and filter to remove insoluble material. Wash the filtrate with diethyl ether and adjust the pH of the aqueous phase to slightly acidic by the addition of a 2 N solution of hydrochloric acid. Extract the mixture with methylene chloride and wash the combined organic phase with brine. Dry over anhydrous sodium sulfate and concentrate under reduced pressure to provide an oil. Re-dissolve the material in methylene chloride and concentrate under a stream of nitrogen to provide 0.44 g (19.2%) of (R)-1-(3-ethoxycarbonyl-phenyl)-pyrrolidine-2-carboxylic acid as an oil.

Workup

  1. temperatureBubble Argon through the mixture for 30 min then heat
  2. customthe reaction to 90° C. for 15 hours
  3. filtrationfilter
  4. customto remove insoluble material
  5. washWash the filtrate with diethyl ether
  6. additionslightly acidic by the addition of a 2 N solution of hydrochloric acid
  7. extractionExtract the mixture with methylene chloride
  8. washwash the combined organic phase with brine
  9. dry with materialDry over anhydrous sodium sulfate
  10. concentrationconcentrate under reduced pressure
  11. customto provide an oil
  12. concentrationRe-dissolve the material in methylene chloride and concentrate under a stream of nitrogen

Sources & evidence

ORD record
ord-846f27f63eab4e738e01c0d6bc095ecb
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

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