Water → Compound 10

HRID 1668684Notes

Reaction equation

HRID 1668684 reaction equation
[N:1]1([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5][CH:4]=[CH:3][CH2:2]1.C[N+]1([O-])CC[O:17]CC1.[OH2:21]>CC(C)=O.[Os](=O)(=O)(=O)=O>[OH:21][C@H:3]1[C@@H:4]([OH:17])[CH2:5][N:1]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:2]1

Participants

6

Reactant 3

HCID 962WaterHCID 82029Methyl morpholine oxideHCID 5148195tert-Butyl 2,5-dihydro-1H-pyrrole-1-carboxylate

Product 1

HCID 13329883Compound 10Yield 77%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolvent

Procedure

A solution of the crude tert-butyl 2,5-dihydro-1H-pyrrole-1-carboxylate mixture (57.5 g; 0.22 mol) in acetone (500 mL) was added dropwise to a mixture of N-methyl morpholine-N-oxide (28.45 g; 0.243 mol), osmium tetroxide (1.0 g; 0.004 mol) and water (500 mL) while keeping the temperature below 25° C. The reaction mixture was then stirred for 5 hours at ambient temperature. Acetone was evaporated off and the organic phase extracted with ethyl acetate. The combined organic phases were washed in turn with water and brine and dried over magnesium sulphate. The solvent was evaporated under vacuum and the residue was purified by column chromatography on silica using increasingly polar solvent mixtures, starting with ethyl acetate/petroleum ether (1/1) and ending with pure ethyl acetate. A second flash chromatography using increasingly polar solvent mixtures, starting with methanol/dichloromethane (2/98) and ending with methanol/dichloromethane (5/95) was done. Evaporation of the solvent gave tert-butyl (3R,4S)-3,4-dihydroxypyrrolidine-1-carboxylate (34.6 g; 77%) as a brown oil.

Workup

  1. customthe temperature below 25° C
  2. customAcetone was evaporated off
  3. extractionthe organic phase extracted with ethyl acetate
  4. washThe combined organic phases were washed in turn with water and brine
  5. dry with materialdried over magnesium sulphate
  6. customThe solvent was evaporated under vacuum
  7. customthe residue was purified by column chromatography on silica using
  8. temperatureincreasingly polar solvent mixtures
  9. temperatureA second flash chromatography using increasingly polar solvent mixtures
  10. customEvaporation of the solvent

Sources & evidence

ORD record
ord-7d4646a4cdad46108c16d2fd9d4cb56b
Source dataset
uspto-grants-2011_08
Patent number
US07989460B2

Reaction notes

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