Imidazole → HCID 59193041, compound

HRID 2388553Notes

Reaction equation

HRID 2388553 reaction equation
[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:10][C@H:11]([CH2:15][CH2:16][OH:17])[C:12]([OH:14])=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].N1C=CN=C1.[CH3:24][C:25]([Si:28](Cl)([CH3:30])[CH3:29])([CH3:27])[CH3:26]>CN(C=O)C>[Si:28]([O:17][CH2:16][CH2:15][C@@H:11]([NH:10][C:4]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=1[CH3:18])[C:12]([OH:14])=[O:13])([C:25]([CH3:27])([CH3:26])[CH3:24])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 59193082HCID 59193082, compound

Product 1

HCID 59193041HCID 59193041, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a 25 mL round-bottomed flask equipped with a magnetic stir bar and a septum was added (R)-2-(3-chloro-4-cyano-2-methylphenylamino)-4-hydroxybutanoic acid (1.49 g, 5.55 mmol). This was dissolved in dry DMF (68 mL) under an atmosphere of nitrogen. This mixture was cooled to 0° C. followed by addition of imidazole (3.02 g, 44.36 mmol) and TBDMSCl (4.18 g, 27.75 mmol). The reaction was allowed to slowly warm to room temperature overnight quenched by slow addition of aqueous ammonium chloride (sat) (60 mL). The solution was extracted with EtOAc (3×100 mL). The combined organic extracts were washed with (5%) aqueous citric acid (100 mL) (×2), water (80 mL) then dried over Na2SO4, filtered, and concentrated under reduced pressure to reveal a yellow oil (4.2 g). This material was used directly in the next step.

Workup

  1. customTo a 25 mL round-bottomed flask equipped with a magnetic stir bar
  2. temperatureto slowly warm to room temperature overnight
  3. customquenched by slow addition of aqueous ammonium chloride (sat) (60 mL)
  4. extractionThe solution was extracted with EtOAc (3×100 mL)
  5. washThe combined organic extracts were washed with (5%) aqueous citric acid (100 mL) (×2), water (80 mL)
  6. dry with materialthen dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-338b036203e94eea9760aa5937cd5edd
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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