Citric Acid → 5-(4-Chlorophenyl)-6-(cyclopropylmethoxy)nicotinic acid

HRID 1929799Notes

Reaction equation

HRID 1929799 reaction equation
Cl[C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[OH:18][CH2:19][CH:20]1[CH2:22][CH2:21]1.[OH-].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C:10]2[C:2]([O:18][CH2:19][CH:20]3[CH2:22][CH2:21]3)=[N:3][CH:4]=[C:5]([CH:9]=2)[C:6]([OH:8])=[O:7])=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 14797Potassium HydroxideHCID 75644CyclopropanemethanolHCID 866191836-Chloro-5-(4-chlorophenyl)-3-pyridinecarboxylic acid

Product 1

HCID 666874825-(4-Chlorophenyl)-6-(cyclopropylmethoxy)nicotinic acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

6-Chloro-5-(4-chloro-phenyl)-nicotinic acid (22.3 g, 0.083 mol) was dissolved in dimethylsulfoxide (130 mL). To this solution was added (hydroxymethyl)cyclopropane (10.1 g, 0.125 mol) and potassium hydroxide powder (18.7 g, 0.333 mol). This mixture was reacted (in ten portions) for 20 min in a microwave at 100° C. The reaction mixture was poured into ice-water (500 mL) and citric acid (10%, 3000 mL) was added with stirring. Stirring was continued for 30 min during which time the product precipitated. The product was filtered off washed with water and dissolved in ethylacetate (1500 mL). The solution was concentrated in vacuo and the title compound crystallized from the concentrated solution as a white solid (21.5 g); MS (ISP) 302.2 (M−H)

Workup

  1. customThis mixture was reacted (in ten portions) for 20 min in a microwave at 100° C
  2. additionwas added
  3. stirringStirring
  4. customthe product precipitated
  5. filtrationThe product was filtered off
  6. washwashed with water
  7. dissolutiondissolved in ethylacetate (1500 mL)
  8. concentrationThe solution was concentrated in vacuo
  9. customthe title compound crystallized from the concentrated solution as a white solid (21.5 g)

Sources & evidence

ORD record
ord-d428956bf4d84dfe80a913763206baa4
Source dataset
uspto-grants-2012_05
Patent number
US08188093B2

Reaction notes

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