Hydrochloric Acid → 2-(7-Methoxyquinolin-4-yloxy)acetic acid

HRID 2176474Notes

Reaction equation

HRID 2176474 reaction equation
[OH-].[K+].[OH:3][CH2:4][C:5]([OH:7])=[O:6].Cl[C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1.Cl>CS(C)=O>[CH3:20][O:19][C:15]1[CH:14]=[C:13]2[C:18]([C:9]([O:3][CH2:4][C:5]([OH:7])=[O:6])=[CH:10][CH:11]=[N:12]2)=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 757Glycolic AcidHCID 14797Potassium HydroxideHCID 106078294-Chloro-7-methoxyquinoline

Product 1

HCID 576910212-(7-Methoxyquinolin-4-yloxy)acetic acidYield 36%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A 250-mL, 3-neck, rb flask equipped with a magnetic stirbar, a reflux condenser and a powder funnel was charged with potassium hydroxide (6.0 g, 90 mmol) then 2-hydroxyacetic acid (5.0 g, 65 mmol) with stirring. The solid reactants gradually reacted and liquified as significant heat was generated. Upon dissolution of all the reagents, flask containing the hot syrupy liquid was immersed in a 170° C. oil bath, then a solution of 4-chloro-7-methoxyquinoline (5.0 g, 26 mmol) in anhydrous DMSO (20 mL, 4 vol wrt quinoline) was added dropwise over 20-30 min via addition funnel. The resulting brown solution was maintained in the oil bath with stirring. After 2.5 h, the flask was removed from the oil bath, then quenched by the addition of water (100 mL, 5 vol wrt DMSO). The resulting brown solution was immersed in an ice bath, and the mixture was neutralized by the dropwise addition of 6 N HCl (15 mL, 1 equiv to KOH), which resulted in the formation of a thick yellow ppt and brought the mixture to pH 3. The mixture was filtered and washed with water and ACN. The solid products were dried under vacuum to yield 2-(7-methoxyquinolin-4-yloxy)acetic acid (2.16 g, 36% yield) as a yellow solid. (ESI, pos. ion) m/z: 234.1 (M+H).

Workup

  1. customA 250-mL, 3-neck, rb flask equipped with a magnetic stirbar, a reflux condenser and a powder funnel
  2. customThe solid reactants gradually reacted
  3. temperatureas significant heat
  4. dissolutionUpon dissolution of all the reagents, flask
  5. additioncontaining the hot syrupy liquid
  6. customwas immersed in a 170° C.
  7. temperatureThe resulting brown solution was maintained in the oil bath
  8. customthe flask was removed from the oil bath
  9. customquenched by the addition of water (100 mL, 5 vol wrt DMSO)
  10. customThe resulting brown solution was immersed in an ice bath
  11. customresulted in the formation of a thick yellow ppt
  12. filtrationThe mixture was filtered
  13. washwashed with water and ACN
  14. customThe solid products were dried under vacuum

Sources & evidence

ORD record
ord-692049214b184a55a4e94b17e655d9eb
Source dataset
uspto-grants-2015_06
Patent number
US09066954B2

Reaction notes

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