Hydrochloric Acid → HCID 69733160, compound

HRID 2183581Notes

Reaction equation

HRID 2183581 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=O.[H-].[Na+].C[Si](C=[N+]=[N-])(C)C.Cl.[C:22]([O:25][CH2:26][CH3:27])(=[O:24])[CH3:23]>C(Cl)Cl.O.CO>[CH3:10][O:9][C:7]([C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Br:1])[CH:11]=1)=[CH:23][C:22]([O:25][CH2:26][CH3:27])=[O:24]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 24758Sodium hydride2×HCID 167693TrimethylsilyldiazomethaneHCID 699336Methyl 5-bromopyridine-3-carboxylate

Product 1

HCID 69733160HCID 69733160, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A solution of methyl 5-bromonicotinate (15.0 g, 69.4 mmol) in ethyl acetate is treated with NaH (60% in mineral oil, 2.4 g) and gently heated at 40° C. until a mild exotherm occurs. After cessation of reflux, the reaction mixture is treated with additional NaH (2.27 g, 139 mmol total), heated at reflux temperature for 16 h, cooled to room temperature and diluted with CH2Cl2 and water. The organic phase is separated, washed with brine, dried over Na2SO4 and concentrated in vacuo. The resultant oil is dissolved in acetonitrile and methanol, treated with a 2M solution of trimethylsilyl diazomethane (TMSCHN2) in hexanes (70 ml, 140 mmol), stirred for 36 h and treated with 5% aqueous HCl. After cessation of nitrogen evolution, the phases are separated and the organic phase is washed with brine, dried over Na2SO4 and concentrated in vacuo. The resultant residue is chromatographed through a plug of silica gel (4:1 hexanes:EtOAc) to give the title compound as a light brown solid, 10.1 g (53% yield), identified by HNMR and mass spectral analyses.

Workup

  1. temperatureAfter cessation of reflux
  2. temperatureheated
  3. temperatureat reflux temperature for 16 h
  4. temperaturecooled to room temperature
  5. customThe organic phase is separated
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. dissolutionThe resultant oil is dissolved in acetonitrile
  10. customAfter cessation of nitrogen evolution, the phases are separated
  11. washthe organic phase is washed with brine
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated in vacuo
  14. customThe resultant residue is chromatographed through a plug of silica gel (4:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-be108c48bdc04855b3841cb51f216d3b
Source dataset
uspto-grants-2005_05
Patent number
US06900223B2

Reaction notes

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