Methyl iodide → HCID 66757096, compound

HRID 855887Notes

Reaction equation

HRID 855887 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:12]([CH3:13])[C:11](=[O:14])[CH2:10][CH:9]1[C:15]([OH:17])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:18]([O-])([O-])=O.[K+].[K+].CI>CN(C)C=O.Cl>[CH3:18][O:16][C:15]([CH:9]1[CH2:10][C:11](=[O:14])[CH:12]([CH3:13])[N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:17]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 66756911HCID 66756911, compound

Product 1

HCID 66757096HCID 66757096, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3.0 g of crude 5-methyl-4-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester in 25 mL of N,N-dimethylformamide was added 1.2 g (8.7 mmol) of K2CO3, and 1.2 mL (19.3 mmol) of methyl iodide. The mixture was stirred at 80° C. for 20 min, cooled to ambient temperature, then diluted with 125 mL of 0.2M HCl(aq.). This was extracted with diethyl ether (3×20 mL), then the combined ether layers were extracted with water (1×20 mL), and brine (1×20 mL), dried over MgSO4, filtered, and concentrated to an oil. The product was purified via silica gel chromatography, eluting with 20% ethyl acetate/hexanes to give the 2,5-cis isomer. The 2,5-trans isomer eluted slightly faster than the desired cis isomer. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.30 (d, J=7.1 Hz, 3H) 1.40 (m, 9H) 2.59 (dd, J=19.2, 3.2 Hz, 1H) 3.12 (dd, J=18.3, 11.2 Hz, 1H) 3.66 (s, 3H) 3.92 (q, J=6.8 Hz, 1H) 4.63 (dd, J=10.7, 3.6 Hz, 1H), NOE observed between H-2 and H-5, not observed in the corresponding trans isomer; MS (ESI) m/z=256 (M−H)+.

Workup

  1. temperaturecooled to ambient temperature
  2. extractionThis was extracted with diethyl ether (3×20 mL)
  3. extractionthe combined ether layers were extracted with water (1×20 mL), and brine (1×20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to an oil
  7. customThe product was purified via silica gel chromatography
  8. washeluting with 20% ethyl acetate/hexanes
  9. customto give the 2,5-cis isomer
  10. washThe 2,5-trans isomer eluted slightly faster than the desired cis isomer

Sources & evidence

ORD record
ord-4c6d05ce85454b3e94e99225faa24bdd
Source dataset
uspto-grants-2007_08
Patent number
US07262207B2

Reaction notes

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