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

HRID 1929836Notes

Reaction equation

HRID 1929836 reaction equation
[Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[OH:12][CH2:13][CH:14]1[CH2:16][CH2:15]1.[OH-].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O.O>[Br:1][C:2]1[C:3]([O:12][CH2:13][CH:14]2[CH2:16][CH2:15]2)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]

Participants

7

Reactant 4

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

Product 1

HCID 211097085-Bromo-6-(cyclopropylmethoxy)nicotinic acidYield 71%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A mixture of 3.0 g (13 mmol) 5-Bromo-6-chloro-nicotinic acid, 1.4 g (19 mmol) (hydroxymethyl)cyclopropane and 2.85 g (51 mmol) potassium hydroxide in DMSO (12 mL) was heated under microwave radiation for 6 min to 100° C. 50 mL water and 150 mL citric acid (10%) was added. A solid precipitated, was filtered off, re-dissolved in ethyl acetate and dried with Na2SO4. The product crystallized upon evaporation of the solvent from ethyl acetate/heptane 1:1 to yield 2.1 g (71%) of the title compound as white solid, MS (ISP): 270.3 (M−H).

Workup

  1. temperaturewas heated under microwave radiation for 6 min to 100° C
  2. customA solid precipitated
  3. filtrationwas filtered off
  4. dissolutionre-dissolved in ethyl acetate
  5. dry with materialdried with Na2SO4
  6. customThe product crystallized upon evaporation of the solvent from ethyl acetate/heptane 1:1

Sources & evidence

ORD record
ord-8eb039814ffd48a28e826c304e8df24c
Source dataset
uspto-grants-2012_05
Patent number
US08188093B2

Reaction notes

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