4-Methylmorpholine → tert-Butyl 2-(2-methoxy-2-oxoethyl)pyrrolidine-1-carboxylate

HRID 538674Notes

Reaction equation

HRID 538674 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.Cl[C:24]([O:26][CH2:27]C(C)C)=[O:25].[N+](=C)=[N-]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH2:13][C:24]([O:26][CH3:27])=[O:25])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9550DiazomethaneHCID 62365Isobutyl chloroformateHCID 2684721-[(Tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 13425758tert-Butyl 2-(2-methoxy-2-oxoethyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 35 (10 g, 46.46 mmol) in dry THF were added drop wise N-methyl morpholine (6.4 mL, 58.1 mmol) and isobutyl chloroformate (6.7 mL, 65.1 mmol) at −30° C. The reaction mixture was stirred at same temperature for one hour and diazomethane solution (prepared in situ) was added at −30° C. The resulting mixture was allowed to stir at rt overnight. Excess diazomethane was quenched with acetic acid (15 mL) and evaporated under reduced pressure. The residue was dissolved in ether and washed with water and brine. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated. The residue was dissolved in methanol (100 mL) and Ag2O (5.5 g) was added portion-wise at ice-cold conditions, and then allowed to stir at rt for 2 hours. Chloroform was added, filtered through Celite® reagent and washed with methanol. The filtrate was concentrated and the crude material was purified by chromatography on silica-gel (230-400 mesh) eluting with 1-5% of ethyl acetate-hexane to get light yellow liquid compound 36.

Workup

  1. stirringto stir at rt overnight
  2. customExcess diazomethane was quenched with acetic acid (15 mL)
  3. customevaporated under reduced pressure
  4. dissolutionThe residue was dissolved in ether
  5. washwashed with water and brine
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. dissolutionThe residue was dissolved in methanol (100 mL)
  10. additionAg2O (5.5 g) was added portion-wise at ice-cold conditions
  11. stirringto stir at rt for 2 hours
  12. additionChloroform was added
  13. filtrationfiltered through Celite® reagent
  14. washwashed with methanol
  15. concentrationThe filtrate was concentrated
  16. customthe crude material was purified by chromatography on silica-gel (230-400 mesh)
  17. washeluting with 1-5% of ethyl acetate-hexane

Sources & evidence

ORD record
ord-a5074ca203434c26bee7daf45a09f9ff
Source dataset
uspto-grants-2014_10
Patent number
US08865741B2

Reaction notes

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