Oxalyl chloride → 5-[2-(4-bromo-2-chloro-phenyl)-acetyl]-1-methyl-1H-pyridin-2-one

HRID 1095983Notes

Reaction equation

HRID 1095983 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[CH:5][C:4]([C:9]([OH:11])=O)=[CH:3]1.C(Cl)(=O)C(Cl)=O.[Br:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25]Br)=[C:21]([Cl:27])[CH:20]=1>C(Cl)Cl.CN(C)C=O.COCCOC.[Zn].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>[Br:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:9]([C:4]2[CH:5]=[CH:6][C:7](=[O:8])[N:2]([CH3:1])[CH:3]=2)=[O:11])=[C:21]([Cl:27])[CH:20]=1

Participants

9

Reactant 3

HCID 65578Oxalyl chlorideHCID 592704N(1)-methyl-2-pyridone-5-carboxylic acidHCID 219144864-Bromo-1-(bromomethyl)-2-chlorobenzene

Product 1

HCID 666994925-[2-(4-bromo-2-chloro-phenyl)-acetyl]-1-methyl-1H-pyridin-2-one

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 23994ZincCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent3×

Procedure

To a suspension of 1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (606 mg) in CH2Cl2 (5 ml) were added one drop of N,N-dimethylformamide and oxalylchloride (803 mg). The mixture was stirred at room temperature for 1.5 h and was then concentrated to dryness. 1,2-Dimethoxyethane was added and the solvent was evaporated again to give the crude acid chloride. To a suspension of zinc powder (517 mg) in 1,2-dimethoxyethane (5 ml) was added tetrakis(triphenylphosphine)palladium(0) (55 mg). A suspension of the acid chloride in 1,2-dimethoxyethane (5 ml) was added. The mixture was cooled in an ice bath and a solution of 4-bromo-1-bromomethyl-2-chloro-benzene (1.125 g) in 1,2-dimethoxyethane (5 ml) was slowly added over 30 min. The mixture was stirred for 30 min at 0° C. and for 1.5 h at room temperature. The mixture was filtered and the filtrate was concentrated. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 7:3=>0:1) to give the title compound (603 mg, not completely pure) as a colorless solid. MS (m/e, ISP neg. ion)=338.0 [M−H+].

Workup

  1. concentrationwas then concentrated to dryness
  2. addition1,2-Dimethoxyethane was added
  3. customthe solvent was evaporated again
  4. customto give the crude acid chloride
  5. additionwas added
  6. temperatureThe mixture was cooled in an ice bath
  7. stirringThe mixture was stirred for 30 min at 0° C. and for 1.5 h at room temperature
  8. filtrationThe mixture was filtered
  9. concentrationthe filtrate was concentrated
  10. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 7:3=>0:1)

Sources & evidence

ORD record
ord-4068df4ef5734bc688ae8a0cd988b004
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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