Formaldehyde → 3-(Benzotriazol-1-ylmethylbenzylamino)propionic acid ethyl ester

HRID 2206260Notes

Reaction equation

HRID 2206260 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1.[CH2:10]([NH:17][CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH2:25]=O>CO>[N:1]1([CH2:25][N:17]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 90196N-(Phenylmethyl)-beta-alanine ethyl esterHCID 178418385HCID 178418385, compound

Product 1

HCID 594427333-(Benzotriazol-1-ylmethylbenzylamino)propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1H-benzotriazole (2.38 g) in methanol (20 mL) were added ethyl N-benzyl-β-alaninate (4.14 g) and aqueous formaldehyde solution (37%, 2 mL) at room temperature. The reaction mixture was stirred overnight at room temperature, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether) to give ethyl N-(1H-benzotriazol-1-ylmethyl)-N-benzyl-β-alaninate (5.60 g). To a mixture of zinc powder (1.74 g) in anhydrous THF (16 mL) was added chlorotrimethylsilane (1.58 g) under nitrogen atmosphere, and the mixture was stirred at room temperature for 10 min. To the reaction mixture was added ethyl bromodifluoroacetate (2.97 g) at room temperature, and then a solution of ethyl N-(1H-benzotriazol-1-ylmethyl)-N-benzyl-β-alaninate (4.50 g) in THF (8 mL) was added thereto at room temperature. The reaction mixture was stirred at room temperature for 18 hr, and added to water. The insoluble substance was removed by the filtration, and the filtrate was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/petroleum ether) to give the title compound (3.23 g).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by silica gel chromatography (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-c28ea158f29e4c30906bd98b70f87565
Source dataset
uspto-grants-2016_06
Patent number
US09371320B2

Reaction notes

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