Benzyl Bromide → 1-tert-Butyl 2-methyl (2S,4R)-4-(benzyloxy)pyrrolidine-1,2-dicarboxylate

HRID 525044Notes

Reaction equation

HRID 525044 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.[H-].[Na+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CN(C)C=O.ClCCl>[CH2:20]([O:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 148639421-tert-Butyl 2-methyl (2S,4R)-4-(benzyloxy)pyrrolidine-1,2-dicarboxylateYield 108.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(2S,4R)-1-tert-Butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (2.65 g, 10.80 mmol) was dissolved in dimethylformamide (75 ml) and cooled in an ice bath. Sodium hydride (60% in hexanes, 0.57 g, 23.75 mmol) was added and stirred for 10 min. To this solution, benzyl bromide (1.39 ml, 11.69 mmol) dissolved in dichloromethane (9 ml) was dropwise added and the reaction mixture was overnight stirred at room temperature. The solvent was evaporated under reduced pressure and the residue redissolved in ethyl acetate. This organic phase was washed with water, dried over magnesium sulphate, filtered and the solvent evaporated under reduced pressure. 3.93 g (77% yield) of the final product were obtained, pure enough to perform the next synthetic step.

Workup

  1. temperaturecooled in an ice bath
  2. additionwas dropwise added
  3. waitthe reaction mixture was overnight
  4. stirringstirred at room temperature
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionthe residue redissolved in ethyl acetate
  7. washThis organic phase was washed with water
  8. dry with materialdried over magnesium sulphate
  9. filtrationfiltered
  10. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-ab52d5dd61e846f0ae04857822bf0910
Source dataset
uspto-grants-2016_05
Patent number
US09340547B2

Reaction notes

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