Pyridine → [6-Chloro-2-(4-methylpyridine-2-Carbonyl)-1H-indol-3-yl]acetic Acid

HRID 396432Notes

Reaction equation

HRID 396432 reaction equation
[NH2:1][C:2]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:3]=1/[CH:4]=[CH:5]/[C:6]([O:8]C)=[O:7].[N:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.ClC([O:24][CH2:25][CH3:26])=O.Cl[CH2:28]Cl>CN(C)C1C=CN=CC=1>[Cl:14][C:12]1[CH:13]=[C:2]2[C:3]([C:4]([CH2:5][C:6]([OH:8])=[O:7])=[C:26]([C:25]([C:16]3[CH:17]=[C:18]([CH3:28])[CH:19]=[CH:20][N:15]=3)=[O:24])[NH:1]2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 10928Ethyl chloroformateHCID 14925557Methyl (2E)-3-(2-amino-4-chlorophenyl)-2-propenoate

Product 1

HCID 9862267[6-Chloro-2-(4-methylpyridine-2-Carbonyl)-1H-indol-3-yl]acetic AcidYield 92%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To a stirred solution of methyl trans-2-amino-4-chlorocinnamate (R. W. Carling et al., J. Med. Chem. 1993, 36, 3397., 32.6 g, 0.15 mol), pyridine (14.9 ml, 0.17 mol) and 4-dimethylaminopridine (0.5 g) in dichloromethane (500 ml) was added dropwise ethyl chloroformate (16.2 ml, 0.17 mol) at room temperature. After stirring for 2h, the mixture was concentrated. The residue was diluted in ethyl acetate (1000 ml) and washed with 10% aqueous citric acid (500 ml). The organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml). After drying (MgSO4) and removal of solvent, the residual solids were recrystallized from ethyl acetate/hexane to give 39.13 g (92%) of the title compound.

Workup

  1. concentrationthe mixture was concentrated
  2. additionThe residue was diluted in ethyl acetate (1000 ml)
  3. washwashed with 10% aqueous citric acid (500 ml)
  4. washThe organic layer was successively washed with water (500 ml), saturated sodium bicarbonate (500 ml), water (500 ml), brine (500 ml)
  5. customAfter drying
  6. custom(MgSO4) and removal of solvent
  7. customthe residual solids were recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-e26c5e150f6941ec9df7cb49da36576a
Source dataset
uspto-grants-2003_08
Patent number
US06608070B1

Reaction notes

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