1-(Pyrrolidin-1-ylmethyl)benzimidazole → 2-Nitro-5-(2-pyrrolidin-1-yl-ethyl)-benzoic acid methyl ester

HRID 591839Notes

Reaction equation

HRID 591839 reaction equation
[N:1]1([CH2:6]N2C3C=CC=CC=3N=C2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:16][O:17][C:18](=[O:30])[C:19]1[CH:24]=[C:23]([CH2:25]Br)[CH:22]=[CH:21][C:20]=1[N+:27]([O-:29])=[O:28]>CN(C)C=O.[Zn]>[CH3:16][O:17][C:18](=[O:30])[C:19]1[CH:24]=[C:23]([CH2:25][CH2:6][N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:22]=[CH:21][C:20]=1[N+:27]([O-:29])=[O:28]

Participants

5

Reactant 2

HCID 2090961-(Pyrrolidin-1-ylmethyl)benzimidazoleHCID 13399988Methyl 5-(bromomethyl)-2-nitrobenzoate

Product 1

HCID 666710792-Nitro-5-(2-pyrrolidin-1-yl-ethyl)-benzoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of zinc powder (1.05 g, 16.05 mmol) and 1-pyrrolidin-1-ylmethyl-1H-benzoimidazole (2.95 g, 14.59 mmol) in N,N-dimethyl formamide (40 mL) under a nitrogen atmosphere was added 5-bromomethyl-2-nitro-benzoic acid methyl ester (4.0 g, 14.59 mmol). The reaction mixture was stirred at room temperature for 24 hours, then quenched at 0° C. with an ice-cold 25% aqueous solution of ammonium hydroxide (108 mL). The stirring was continued until most of the solid had dissolved. Undissolved solid was filtered off and the filtrate was extracted with diethyl ether. The combined organic layers were washed with 1 N aqueous sodium hydroxide, then water, and were dried over anhydrous sodium sulfate and concentrated under high vacuum to give 2-nitro-5-(2-pyrrolidin-1-yl-ethyl)-benzoic acid methyl ester as an orange oil. Yield: 1.3 g (32%). The crude material was used for the next step without further purification.

Workup

  1. customquenched at 0° C. with an ice-cold 25% aqueous solution of ammonium hydroxide (108 mL)
  2. dissolutionhad dissolved
  3. filtrationwas filtered off
  4. extractionthe filtrate was extracted with diethyl ether
  5. washThe combined organic layers were washed with 1 N aqueous sodium hydroxide
  6. dry with materialwater, and were dried over anhydrous sodium sulfate
  7. concentrationconcentrated under high vacuum

Sources & evidence

ORD record
ord-9dabe5a7f7604fb9ae05b4658ab02e7a
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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