Acetic Acid → 3-Amino-5-bromo-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzamide

HRID 1423258Notes

Reaction equation

HRID 1423258 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:18]=[C:19]([N+:21]([O-])=O)[CH:20]=1)[C:5]([NH:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH3:17])=[O:6].CC(O)=O.C(OCC)C>C1COCC1.[Pt]>[NH2:21][C:19]1[CH:18]=[C:4]([CH:3]=[C:2]([Br:1])[CH:20]=1)[C:5]([NH:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH3:17])=[O:6]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 3283Diethyl EtherHCID 904220083-Bromo N (2 (2 (2 methoxyethoxy)ethoxy)ethyl)-5-nitrobenzamide

Product 1

HCID 904220913-Amino-5-bromo-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)benzamideYield 90%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The product from step (i) above (1 kg, 2.56 mol) was dissolved in THF (3.5 L) and AcOH (500 mL) and hydrogenated at 3 MPa (30 bar) H2 at up to 60° C. with 5% Pt/C (30 g of JM type 18 MA, 55% water). Analysis after 5 hrs showed a 1:1 ratio of ArNHOH and ArNH2. The reaction reached completion after being left overnight, with 1H NMR analysis showing 3% des-bromo side product. The catalyst was filtered off, then the residue was diluted with ethyl acetate (3 L) and washed with 20% potassium carbonate solution (3.5 L). The organics were then dried, filtered and concentrated in vacuo to provide a residue that was then slurried in 5 volumes of diethyl ether overnight to reduce the level of the des-bromo species (<2% after the slurry). The sub-title compound was obtained in 90% yield with a purity of 86% by LC.

Workup

  1. customup to 60° C.
  2. waitafter being left overnight, with 1H NMR analysis
  3. filtrationThe catalyst was filtered off
  4. additionthe residue was diluted with ethyl acetate (3 L)
  5. washwashed with 20% potassium carbonate solution (3.5 L)
  6. customThe organics were then dried
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a residue that

Sources & evidence

ORD record
ord-4a53bd25161d4feaaef6526f2a398734
Source dataset
uspto-grants-2015_01
Patent number
US08927563B2

Reaction notes

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