Sodium hydride → HCID 86741174, compound

HRID 1249548Notes

Reaction equation

HRID 1249548 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[C:4]1[CH2:8][C:9]1[CH:17]=[CH:16][C:12]([NH:13][CH:14]=[O:15])=[CH:11][CH:10]=1.Br[CH:19]([CH3:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21]>CN(C)C=O>[CH2:23]([O:22][C:20](=[O:21])[C@H:19]([CH3:25])[N:13]([CH:14]=[O:15])[C:12]1[CH:11]=[CH:10][C:9]([CH2:8][C:4]2[NH:3][CH:7]=[CH:6][N:5]=2)=[CH:17][CH:16]=1)[CH3:24]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79040Ethyl 2-bromopropionateHCID 86741173HCID 86741173, compound

Product 1

HCID 86741174HCID 86741174, compoundYield 52.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

In a 200 ml round-bottom flask is placed a solution of 8.0 g of p-(1-imidazolylmethyl)aniline prepared as described in Reference Example 3, and 30 ml of formic acid in 80 ml of toluene. The flask was fitted with a water separator, and the solution was refluxed for 4 hours. After concentration under reduced pressure, the residual solid was recrystallized from ethanol-diethyl ether to give 6.4 g of p-(1-imidazolylmethyl)-N-formylaniline as colorless prisms. M.P.: 121°-123° C. To a suspension of 0.48 g of 50% sodium hydride in 50 ml of dry dimethylformamide was added 2.01 g of the formylaniline and mixture was heated to 100° C. A solution of 1.81 g of ethyl α-bromopropionate in 30 ml of dry dimethylformamide was added to the mixture and the reaction mixture was heated at 100° C. for 16 hours. After removal of the solvent under reduced pressure, 50 ml of dichloromethane was added to the residue, and the solution was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was chromatographed on silica gel using dichloromethane-ethanol (20:1 by volume) to give 1.58 g of N-formyl-N-[p-(1-imidazolylmethyl)phenyl]alanine ethyl ester as a pale brown oil. Then, a solution of 1.58 g of the resulting ester and 5 ml of concentrated hydrochloric acid in 50 ml of ethanol was stirred for 40 hours at room temperature. After concentration under reduced pressure, the residual solid was recrystallized from ethanol-diethyl ether to give 1.18 g of N-[p-(1-imidazolylmethyl)phenyl]alanine ethyl ester dihydrochloride as pale yellow crystals. M.P.: 154°-159° C.

Workup

  1. temperaturethe reaction mixture was heated at 100° C. for 16 hours
  2. customAfter removal of the solvent under reduced pressure, 50 ml of dichloromethane
  3. additionwas added to the residue
  4. washthe solution was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-3edf84a945744b4baf58178475c289f6
Source dataset
uspto-grants-1986_12
Patent number
US04632934

Reaction notes

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