Ammonium Chloride → 2-[5-Formyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71841Notes

Reaction equation

HRID 71841 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[N:14]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:15](Br)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[Cl-].[NH4+].[C:34](=O)(O)[O-:35].[Na+]>C1COCC1.CN(C=O)C.CCCCCC>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[N:14]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:15]([CH:34]=[O:35])=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 574202132-[5-Bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 723380662-[5-Formyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 45%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

2-[5-Bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (3.804 g, 8.52 mmol) was dissolved in THF (42 mL) and cooled to −78° C. n-BuLi (3.4 mL of a 2.5 M hexane solution, 8.52 mmol) was added dropwise over 3 min. After 65 min, DMF (4 mL) was added and the reaction mixture was warmed to RT. After stirring at RT for 75 min, a saturated aqueous solution of ammonium chloride (50 mL) was added and the entire content of the flask was poured into saturated aqueous sodium bicarbonate. The aqueous phase was extracted 3 times with diethyl ether. The combined organic layers were dried over magnesium sulfate, concentrated and purified by silica column chromatography (30% to 70% EtOAc/hexanes) to provide 2-[5-Formyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.50 g, 45%).

Workup

  1. additionwas added dropwise over 3 min
  2. extractionThe aqueous phase was extracted 3 times with diethyl ether
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. concentrationconcentrated
  5. custompurified by silica column chromatography (30% to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-55be6010c9cd48028572e250956aa1b2
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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