Imidazole → HCID 69995641, compound

HRID 431753

Reaction equation

HRID 431753 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[C@@H:4]([C:17]([OH:19])=[O:18])[CH2:3]1.N1C=CN=C1.[CH3:25][C:26]([Si:29](Cl)([CH3:31])[CH3:30])([CH3:28])[CH3:27]>CN(C=O)C.CCOC(C)=O.CCCCCC>[Si:29]([O:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:8])[C@@H:4]([C:17]([OH:19])=[O:18])[CH2:3]1)([C:26]([CH3:28])([CH3:27])[CH3:25])([CH3:31])[CH3:30]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 688416(2R,4R)-1-((benzyloxy)carbonyl)-4-hydroxypyrrolidine-2-carboxylic acid

Product 1

HCID 69995641HCID 69995641, compoundYield 89.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a mixture of cis4-hydroxy-N-benzyloxycarbonyl-D-proline (18.74 g) and imidazole (11.56 g) in DMF (100 mL) was added TBDMSCl (23.36 g) at 5° C. After stirring at room temperature for 16 hours, the reaction mixture was diluted with EtOAc-hexane (1:1, 600 mL), washed with 1N HCl, water and brine, dried (MgSO4), and evaporated in vacuo. The residue was dissolved in MeOH-THF (3:1, 400 mL). To the solution was added an aqueous solution (100 mL) of K2CO3 (9.77 g) at 5° C., and the mixture was stirred at the same temperature for 1 hour. The organic solvent was evaporated, and the residue was adjusted to pH 2 by the addition of 3N HCl, and extracted with EtOAc. The organic layer was washed with water and brine, dried (MgSO4), and evaporated in vacuo. The residue was purified by silica gal column chromatography to give cis-4-(tert-butyldimethylsilyloxy)-N-benzyloxycarbonyl-D-proline (23.99 g).

Workup

  1. washwashed with 1N HCl, water and brine
  2. dry with materialdried (MgSO4)
  3. customevaporated in vacuo
  4. dissolutionThe residue was dissolved in MeOH-THF (3:1, 400 mL)
  5. additionTo the solution was added an aqueous solution (100 mL) of K2CO3 (9.77 g) at 5° C.
  6. stirringthe mixture was stirred at the same temperature for 1 hour
  7. customThe organic solvent was evaporated
  8. additionthe residue was adjusted to pH 2 by the addition of 3N HCl
  9. extractionextracted with EtOAc
  10. washThe organic layer was washed with water and brine
  11. dry with materialdried (MgSO4)
  12. customevaporated in vacuo
  13. customThe residue was purified by silica gal column chromatography

Sources & evidence

ORD record
ord-ce1db149d5d3404ab6fb24f15fa37f3a
Source dataset
uspto-grants-2003_12
Patent number
US06660759B1

Linked notes

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