Dimethylformamide → HCID 59610693, compound

HRID 1099216Notes

Reaction equation

HRID 1099216 reaction equation
C([Li])CCC.Br[C:7]1[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:10]([C@@H:20]2[CH2:24][CH2:23][CH2:22][N:21]2[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[N:9][CH:8]=1.CN(C)[CH:34]=[O:35]>O1CCCC1>[CH:34]([C:7]1[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:10]([C@@H:20]2[CH2:24][CH2:23][CH2:22][N:21]2[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[N:9][CH:8]=1)=[O:35]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 59610804HCID 59610804, compoundHCID 178418339Butyllithium

Product 1

HCID 59610693HCID 59610693, compoundYield 33.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (2.5 M) in hexanes (1.6 mL, 4.00 mmol) was added dropwise to a stirring solution of (S)-tert-butyl 2-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (prepared by methods described in WO 2008/021928, WO 2008/021936 and WO 2008/021927)(1.70 g, 3.81 mmol) in tetrahydrofuran (20 mL) at −78° C. The reaction mixture was stirred at −78° C. for 7 min, and then quenched with dimethylformamide (0.59 mL, 7.6 mmol) in one portion. The mixture was warmed to room temperature by removing the cooling bath, allowed to stir for 1 h, diluted with water and extracted with ethyl acetate (2×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (0 to 100% ethyl acetate in hexanes) to afford (S)-tert-butyl 2-(5-formyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (500 mg, 1.26 mmol, 33% yield) as a yellow oil and a 2:3 mixture of regioisomers.

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. customby removing the cooling bath
  3. stirringto stir for 1 h
  4. additiondiluted with water
  5. extractionextracted with ethyl acetate (2×)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (0 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d55f4adbb6944868b17686dbfeaf1974
Source dataset
uspto-grants-2012_03
Patent number
US08143414B2

Reaction notes

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