Ammonium Chloride → Ethyl 5-bromo-1H-pyrrolo[2,3-c]pyridine-2-carboxylate

HRID 1693364Notes

Reaction equation

HRID 1693364 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[C:5](=O)[CH2:6][C:7]1[C:12]([N+:13]([O-])=O)=[CH:11][N:10]=[C:9]([Br:16])[CH:8]=1)[CH3:2].[Cl-].[NH4+]>C1COCC1.C(O)C.[Fe]>[CH2:1]([O:3][C:4]([C:5]1[NH:13][C:12]2=[CH:11][N:10]=[C:9]([Br:16])[CH:8]=[C:7]2[CH:6]=1)=[O:18])[CH3:2]

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 597536233-(2-Bromo-5-nitropyridin-4-yl)-2-oxopropionic acid ethyl ester

Product 1

HCID 50998338Ethyl 5-bromo-1H-pyrrolo[2,3-c]pyridine-2-carboxylate

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Route A: To a solution of 3-(2-bromo-5-nitropyridin-4-yl)-2-oxopropionic acid ethyl ester (Preparation 25, 3.38 g, 10.7 mmol) in THF (50 mL) and ethanol (100 mL) was added saturated ammonium chloride solution (50 mL) and iron powder (3.57 g, 64.0 mmol) and the reaction heated under reflux for 2 h. The reaction mixture was filtered through celite and washed several times with ethyl acetate. The solvent was removed in vacuo and the remainder partitioned between saturated sodium hydrogen carbonate solution (100 mL) and ethyl acetate (3×150 mL). The combined organic fractions were dried (MgSO4) and concentrated in vacuo to give the title compound as a brown solid. δH (CD3OD): 1.42 (3H, t), 4.43 (2H, q), 7.14 (1H, s), 7.85 (1H, s), 8.58 (1H, s); m/z (ES+)=269 [M+H]+. Route B: To a solution of 2-bromo-4-methyl-5-nitropyridine (Preparation 24, 5.7 g, 26.3 mmol) in diethyl oxalate (17.9 mL) under argon was added 1,8-diazabicyclo[5,4,0]undec-7-ene (4.5 mL, 30.2 mmol) to give a dark red precipitate. Reaction mixture was stirred at rt for 4.5 h and concentrated in vacuo. Acetic acid (140 mL) was added to the residue under argon and heated to 60° C. Iron (2.94 g, 52.6 mmol) was added in small portions over a period of 1 h. The reaction mixture was heated at 80° C. for 4 h. The reaction mixture was cooled to rt and poured into water (300 mL) which gave a beige precipitate. The precipitate was isolated and washed with water. The solid obtained was dissolved in ethyl acetate (700 ml) and filtered. The filtrate was concentrated in vacuo to give the title compound. m/z (ES+)=269 [M+H]+; RT=3.39 min.

Workup

  1. temperaturethe reaction heated
  2. temperatureunder reflux for 2 h
  3. filtrationThe reaction mixture was filtered through celite
  4. washwashed several times with ethyl acetate
  5. customThe solvent was removed in vacuo
  6. customthe remainder partitioned between saturated sodium hydrogen carbonate solution (100 mL) and ethyl acetate (3×150 mL)
  7. dry with materialThe combined organic fractions were dried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1fec5bc58fd341ca986256dd9ce8792c
Source dataset
uspto-grants-2012_04
Patent number
US08158622B2

Reaction notes

Loading…