Dibromomethane → Tert-butyl 3,4-methylenedioxypyrrolidine-1-carboxylate

HRID 1668685Notes

Reaction equation

HRID 1668685 reaction equation
[OH:1][C@H:2]1[C@@H:6]([OH:7])[CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[H-].[Na+].Br[CH2:18]Br>CN(C=O)C>[O:1]1[CH:2]2[CH2:3][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5][CH:6]2[O:7][CH2:18]1

Participants

5

Reactant 3

HCID 3024DibromomethaneHCID 24758Sodium hydrideHCID 13329883Compound 10

Product 1

HCID 59682912Tert-butyl 3,4-methylenedioxypyrrolidine-1-carboxylateYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
2.5 °C

Procedure

tert-Butyl (3R,4S)-3,4-dihydroxypyrrolidine-1-carboxylate (34.6 g; 0.17 mol) was dissolved in DMF (400 mL) under argon and cooled down to 0-5° C. Sodium hydride (15 g; 0.375 mol) was added portionwise. The reaction mixture formed a foam which was difficult to stir. After 1 hour at 5° C., dibromomethane (15.6 mL; 0.22 mol) was added. After an additional 30 minutes at the same temperature, the reaction mixture was left to rise to ambient temperature. The temperature rose to 35° C. and was stirred overnight. The DMF was evaporated off and the residue partitioned between ethyl acetate and water. The water phase was extracted with ethyl acetate, the organic phases were combined and washed with water, brine, dried over magnesium sulphate and evaporated. The residue was dissolved in a minimum of dichloromethane and purified by flash chromatography using ethyl acetate/petroleum ether (3/7). Evaporation of the solvent gave tert-butyl tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate (19.77 g; 54%) as a colorless oil.

Workup

  1. customThe reaction mixture formed a foam which
  2. waitAfter an additional 30 minutes at the same temperature
  3. waitthe reaction mixture was left
  4. customto rise to ambient temperature
  5. customrose to 35° C.
  6. stirringwas stirred overnight
  7. customThe DMF was evaporated off
  8. customthe residue partitioned between ethyl acetate and water
  9. extractionThe water phase was extracted with ethyl acetate
  10. washwashed with water, brine
  11. dry with materialdried over magnesium sulphate
  12. customevaporated
  13. dissolutionThe residue was dissolved in a minimum of dichloromethane
  14. custompurified by flash chromatography
  15. customEvaporation of the solvent

Sources & evidence

ORD record
ord-e397ee16732f4b75bf3c211202776320
Source dataset
uspto-grants-2011_08
Patent number
US07989460B2

Reaction notes

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