Lithium Chloride → methyl 4-acetyl-1-(3-chloropyridin-2-yl)-1H-pyrrole-2-carboxylate

HRID 874190Notes

Reaction equation

HRID 874190 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[N:5]([C:7]2[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][N:8]=2)[CH:6]=1.[CH2:18]([O:20]C([Sn](CCCC)(CCCC)CCCC)=C)[CH3:19].[Cl-].[Li+]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:18]([C:2]1[CH:3]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[N:5]([C:7]2[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][N:8]=2)[CH:6]=1)(=[O:20])[CH3:19]

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 66659078methyl 4-bromo-1-(3-chloropyridin-2-yl)-1H-pyrrole-2-carboxylate

Product 1

HCID 67125231methyl 4-acetyl-1-(3-chloropyridin-2-yl)-1H-pyrrole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Under argon, 5.0 g (15.6 mmol) of methyl 4-bromo-1-(3-chloropyridin-2-yl)-1H-pyrrole-2-carboxylate were dissolved in THF, and 8.2 g (21.9 mmol) of (1-ethoxyvinyl)tributylstannane, 2.1 g of lithium chloride and 0.9 g (0.8 mmol) of tetrakis(triphenylphosphine)palladium were added at room temperature and the mixture was stirred under reflux for 48 h. The solvent was then distilled off, and the residue was taken up in 200 ml of THF and stirred in the presence of 12 ml of 2N hydrochloric acid at RT for a further 24 h. Once more, the solvent was distilled off, and the residue was dissolved in 120 ml of methyl tert-butyl ether and, at RT, stirred vigorously with 120 ml of saturated potassium fluoride solution for 1 h. The organic phase was separated off and concentrated. The desired product was isolated by chromatographic purification.

Workup

  1. temperatureunder reflux for 48 h
  2. distillationThe solvent was then distilled off
  3. stirringstirred in the presence of 12 ml of 2N hydrochloric acid at RT for a further 24 h
  4. distillationOnce more, the solvent was distilled off
  5. dissolutionthe residue was dissolved in 120 ml of methyl tert-butyl ether and, at RT
  6. stirringstirred vigorously with 120 ml of saturated potassium fluoride solution for 1 h
  7. customThe organic phase was separated off
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-63fa5adf343e49718d8e0bc5c181e19d
Source dataset
uspto-grants-2015_03
Patent number
US08980886B2

Reaction notes

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