Imidazole → HCID 21636779, compound

HRID 434074Notes

Reaction equation

HRID 434074 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[Si:22](Cl)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23].CO>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 887MethanolHCID 28928tert-Butyldimethylsilyl chlorideHCID 14037017(2S,3S)-1-(tert-Butoxycarbonyl)-3-hydroxypyrrolidine-2-carboxylic acid

Product 1

HCID 21636779HCID 21636779, compoundYield 205.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A cooled (0° C.) solution of 30A (15.0 g, 64.8 mmol) and imidazole (22.0 g, 324 mmol) in dry DMF (110 ml) was treated with tert-butyldimethylsilyl chloride (24.3 g, 162 mmol), warmed to RT and stirred for 24 h. The reaction mixture was treated with methanol (150 ml), stirred at RT for another 24 h then partitioned between 10% aqueous citric acid (225 ml) and EtOAc (3×1.0 L). The extracts were washed with brine (200 ml), dried (Na2SO4) and filtered. The filtrate was concentrated to dryness to give a thick colorless syrup (46.0 g). Purification of a portion (20 g) by using automated flash chromatography (135 g silica gel column, EtOAc/hexane gradient) gave the title compound as a thick clear syrup (9.7 g, 99.7%).

Workup

  1. stirringstirred at RT for another 24 h
  2. customthen partitioned between 10% aqueous citric acid (225 ml) and EtOAc (3×1.0 L)
  3. washThe extracts were washed with brine (200 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated to dryness

Sources & evidence

ORD record
ord-de9570d230274c53aa78ade6f6f910b3
Source dataset
uspto-grants-2003_12
Patent number
US06670386B2

Reaction notes

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