Hydrogen Peroxide → 4-Hydroxymethyl-pyrrolidine-1,2-dicarboxylic acid di-tert-butyl ester

HRID 1442972Notes

Reaction equation

HRID 1442972 reaction equation
CC(=CC)C.B.[O:7]1CCCC1.[C:12]([O:16][C:17]([N:19]1[CH2:23][C:22](=[CH2:24])[CH2:21][CH:20]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[O:18])([CH3:15])([CH3:14])[CH3:13].[OH-].[Na+].OO>O1CCCC1.O>[C:12]([O:16][C:17]([N:19]1[CH2:23][CH:22]([CH2:24][OH:7])[CH2:21][CH:20]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[O:18])([CH3:15])([CH3:14])[CH3:13]

Participants

8

Reactant 5

HCID 784Hydrogen PeroxideHCID 105532-Methyl-2-buteneHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 189679044-Methylene-pyrrolidine-1,2-dicarboxylic acid di-tert-butyl ester

Product 1

HCID 189679154-Hydroxymethyl-pyrrolidine-1,2-dicarboxylic acid di-tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of 2-methyl-2-butene (2M in tetrahydrofuran, 30 ml, 60 mmol) in anhydrous tetrahydrofuran (40 ml) at 0° C. under a nitrogen atmosphere was added borane-tetrahydrofuran complex (1M in tetrahydrofuran, 30 ml, 30 mmol) dropwise over 10 minutes and allowed to stir for 2 hours. The reaction mixture was cooled to −20° C. and a solution of 4-methylene-pyrrolidine-1,2-dicarboxylic acid di-tert-butyl ester (2.84 g, 10 mmol) (CAS reg 163 190-46-3) in tetrahydrofuran (20 ml) was added dropwise and stirred to room temperature over 18 hours. Water (40 ml) was added cautiously followed by sodium hydroxide (0.5M, 20 ml) then hydrogen peroxide (27.5% w/w in water, 10 ml) and stirred at room temperature for 2 hours. The organic solvent was removed under reduced pressure and the aqueous extracted with ethyl acetate (2×60 ml). The combined extracts were dried (MgSO4), filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with 40% ethyl acetate/heptane to give the title compound as a mixture of diastereomers (˜5:1 2S,4S:2S,4R) as a colourless oil (1.25 g, 41%)

Workup

  1. stirringstirred to room temperature over 18 hours
  2. customThe organic solvent was removed under reduced pressure
  3. extractionthe aqueous extracted with ethyl acetate (2×60 ml)
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified by chromatography on silica gel
  8. washeluting with 40% ethyl acetate/heptane

Sources & evidence

ORD record
ord-5c0bb3cf35fa4b7ab0c848dd77db62e1
Source dataset
uspto-grants-2010_02
Patent number
US07659305B2

Reaction notes

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