2-Chloro-6-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-nicotinic acid methyl ester → Methyl 6-amino-2-chloronicotinate

HRID 1442785Notes

Reaction equation

HRID 1442785 reaction equation
[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2C(=O)C3C(=CC=CC=3)C2=O)=[N:6][C:5]=1[Cl:21]>N.CO>[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[N:6][C:5]=1[Cl:21]

Participants

3

Reactant 1

HCID 591658812-Chloro-6-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-nicotinic acid methyl ester

Product 1

HCID 59165988Methyl 6-amino-2-chloronicotinateYield 90%

Reagents, catalysts & solvents 1

HCID 21705897Ammonia methanolSolvent

Procedure

A solution of 2-chloro-6-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-nicotinic acid methyl ester (1.0 g, 3.2 mmol) in NH3/MeOH (3M, 50 mL) was stirred at room temperature overnight. The solvent was removed under vacuum and the residue was dissolved in methylene chloride (50 mL), and was washed with saturated aqueous Na2CO3 and water. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel (methylene chloride) to give amino-2-chloronicotinic acid methyl ester (0.53 g, 90%). 1H NMR (400 MHz, DMSO) δ 7.86 (d, J=8.8 Hz, 1H), 7.15 (brs, 2H), 6.38 (d, J=8.4 Hz, 1H), 3.72 (s, 3H).

Workup

  1. customThe solvent was removed under vacuum
  2. dissolutionthe residue was dissolved in methylene chloride (50 mL)
  3. washwas washed with saturated aqueous Na2CO3 and water
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by flash column chromatography on silica gel (methylene chloride)

Sources & evidence

ORD record
ord-3b9498694a6843929cceb15b869bcb79
Source dataset
uspto-grants-2010_02
Patent number
US07659268B2

Reaction notes

Loading…