Hydrochloric Acid → 5-Bromo-6-(2-methoxy-ethoxy)-nicotinic acid

HRID 1929847Notes

Reaction equation

HRID 1929847 reaction equation
C[O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([Br:10])[C:7](Cl)=[N:6][CH:5]=1.[CH3:13][O:14][CH2:15][CH2:16][OH:17].C1CCN2C(=NCCC2)CC1.[OH-].[K+].Cl>O>[Br:10][C:8]1[C:7]([O:17][CH2:16][CH2:15][O:14][CH3:13])=[N:6][CH:5]=[C:4]([CH:9]=1)[C:3]([OH:2])=[O:12]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 80192-MethoxyethanolHCID 14797Potassium HydroxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2764313Methyl 5-bromo-6-chloronicotinate

Product 1

HCID 211097055-Bromo-6-(2-methoxy-ethoxy)-nicotinic acidYield 66%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 325 mg (1.3 mmol) 5-bromo-6-chloro-nicotinic acid methyl ester, 233 mg (3.24 mmol) 2-methoxyethanol and 493 mg (3.24 mmol) DBU was heated under microwave radiation for 2 min to 180° C. 0.65 mL water and 0.49 mL 5N KOH aq. was added and the mixture was heated under microwave radiation for 2 min to 160° C. The mixture was acidified with 1N HCl aq. and extracted with ethyl acetate. After evaporation the residue was purified by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile/water/HCOOH. The combined product fractions were evaporated to yield 237 mg (66%) of the title compound as white solid. MS (ISP): 274 (M−H).

Workup

  1. temperaturewas heated under microwave radiation for 2 min to 180° C
  2. temperaturethe mixture was heated under microwave radiation for 2 min to 160° C
  3. extractionextracted with ethyl acetate
  4. customAfter evaporation the residue
  5. customwas purified by preparative HPLC on reversed phase
  6. washeluting with a gradient
  7. customformed from acetonitrile/water/HCOOH
  8. customThe combined product fractions were evaporated

Sources & evidence

ORD record
ord-abdcf922e8ca43058a55618b9c778e7a
Source dataset
uspto-grants-2012_05
Patent number
US08188093B2

Reaction notes

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