Triethylamine → HCID 131731313, compound

HRID 2364956Notes

Reaction equation

HRID 2364956 reaction equation
C[O:2][C:3]1[N:8]=[C:7]([C:9]([O:11]C)=[O:10])[CH:6]=[CH:5][C:4]=1[N:13]1[CH:17]=[C:16]([CH3:18])[N:15]=[CH:14]1.[Br:19]C1N=C(OC)C(N2C=C(C)N=C2)=CC=1.C(N(CC)CC)C>CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[BrH:19].[CH3:18][C:16]1[N:15]=[CH:14][N:13]([C:4]2[C:3](=[O:2])[NH:8][C:7]([C:9]([OH:11])=[O:10])=[CH:6][CH:5]=2)[CH:17]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 576093006-bromo-2-methoxy-3-(4-methyl-1H-imidazol-1-yl)pyridineHCID 67798582Methyl 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridine-2-carboxylate

Product 1

HCID 131731313HCID 131731313, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

Synthesis of methyl 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridine-2-carboxylate (C2). To a solution of the known 6-bromo-2-methoxy-3-(4-methyl-1H-imidazol-1-yl)pyridine (C1, T. Kimura et al., U.S. Pat. Appl. Publ. (2009), US 20090062529 A1) (44.2 g, 165 mmol) in methanol (165 mL) was added triethylamine (46 mL, 330 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloromethane complex (6.7 g, 8.24 mmol). The mixture was degassed several times with nitrogen. The reaction was heated to 70° C. under CO atmosphere (3 bar) in a Parr apparatus. After 30 minutes, the pressure dropped to 0.5 bar; additional CO was added until the pressure stayed constant for a period of 30 minutes. The mixture was allowed to cool to room temperature and filtered through a pad of Celite. The Celite pad was washed twice with methanol and the combined filtrates were concentrated under reduced pressure. The residue (88 g) was dissolved in ethyl acetate (1 L) and water (700 mL), and the layers were separated. The organic layer was washed with water (200 mL), and the aqueous layer was extracted with ethyl acetate (500 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to provide the title compound. Yield: 42.6 g, 175 mmol, quantitative.

Workup

  1. customThe mixture was degassed several times with nitrogen
  2. additionthe pressure dropped to 0.5 bar
  3. additionadditional CO was added until the pressure
  4. waitstayed constant for a period of 30 minutes
  5. temperatureto cool to room temperature
  6. filtrationfiltered through a pad of Celite
  7. washThe Celite pad was washed twice with methanol
  8. concentrationthe combined filtrates were concentrated under reduced pressure
  9. dissolutionThe residue (88 g) was dissolved in ethyl acetate (1 L)
  10. customwater (700 mL), and the layers were separated
  11. washThe organic layer was washed with water (200 mL)
  12. extractionthe aqueous layer was extracted with ethyl acetate (500 mL)
  13. dry with materialThe combined organic layers were dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-682f1d037c854b6d95456f1407239de6
Source dataset
uspto-grants-2014_04
Patent number
US08697673B2

Reaction notes

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