Citric Acid → 5-Bromo-6-(cyclopropylmethoxy)nicotinic acid

HRID 1766507Notes

Reaction equation

HRID 1766507 reaction equation
[OH-].[K+].[Br:3][C:4]1[CH:5]=[C:6]([C:11]([OH:13])=[O:12])[CH:7]=[N:8][C:9]=1Cl.[CH:14]1([CH2:17][OH:18])[CH2:16][CH2:15]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O.CCCCCCC.C(OC(=O)C)C.O>[Br:3][C:4]1[C:9]([O:18][CH2:17][CH:14]2[CH2:16][CH2:15]2)=[N:8][CH:7]=[C:6]([CH:5]=1)[C:11]([OH:13])=[O:12]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 14797Potassium HydroxideHCID 75644CyclopropanemethanolHCID 2854335-Bromo-6-chloropyridine-3-carboxylic acid

Product 1

HCID 211097085-Bromo-6-(cyclopropylmethoxy)nicotinic acidYield 69.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

Potassium hydroxide (3.8 g, 51 mmol) was added to a solution of 5-bromo-6-chloro-3-pyridinecarboxylic acid (CAS 29241-62-1; 3 g, 13 mmol) and cyclopropanemethanol (1.5 mL, 19 mmol) in dimethylsulfoxide (12 mL). The mixture was microwaved at 100° C. for 4 min and poured into a mixture of water (50 mL) and citric acid (150 mL, 10%). The precipitating solid was collected by filtration, washed with water, dissolved in ethyl acetate and dried with Na2SO4. The solvent was removed to yield a solid which was stirred with a mixture of heptane/ethylacetate (40 mL, 1:1), filtered, washed with heptane and dried to yield 2.45 g of the title compound as colorless solid, MS (ISP) 270.1, 272.1 (M−H)−.

Workup

  1. customThe mixture was microwaved at 100° C. for 4 min
  2. filtrationThe precipitating solid was collected by filtration
  3. washwashed with water
  4. dissolutiondissolved in ethyl acetate
  5. dry with materialdried with Na2SO4
  6. customThe solvent was removed
  7. customto yield a solid which
  8. filtrationfiltered
  9. washwashed with heptane
  10. customdried

Sources & evidence

ORD record
ord-ef9c3a3bbc6c429bb65fa210371000e0
Source dataset
uspto-grants-2007_06
Patent number
US07229999B2

Reaction notes

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