Reaction #2286282

Reaction equation

[4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester

[4-(6-Chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester

sodium hydroxide

→

[4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid

[4-(6-Chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid

Solvents

methanol

Conditions

Workup

1. 1
   Otherat room temperature
2. 2
   ConcentrationAt this time, the reaction mixture was concentrated under vacuum
3. 3
   workup.ADDITIONThe resulting solid was diluted with water (200 mL)
4. 4
   Extractionextracted with ethyl acetate (200 mL)
5. 5
   workup.ADDITIONThe water layer was acidified to pH=4 by the addition of a 1N aqueous hydrochloric acid solution
6. 6
   Extractionwas extracted with ethyl acetate (2×200 mL)
7. 7
   Washwashed with a saturated aqueous sodium chloride solution
8. 8
   Dryingdried with magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated under vacuum
11. 11
    Otherto afford a solid
12. 12
    OtherThe solid was dried overnight under high vacuum

Procedure

A solution of [4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester (8a) (1.66 g, 4.75 mmol, contains a minor amount of isomer) in methanol (50 mL) at room temperature was treated dropwise with a 1N aqueous sodium hydroxide solution (9.5 mL, 9.50 mmol). The reaction was stirred at room temperature for 24 h. At this time, the reaction mixture was concentrated under vacuum. The resulting solid was diluted with water (200 mL) and extracted with ethyl acetate (200 mL). The ethyl acetate layer was discarded. The water layer was acidified to pH=4 by the addition of a 1N aqueous hydrochloric acid solution and was extracted with ethyl acetate (2×200 mL). The organic layers were combined, washed with a saturated aqueous sodium chloride solution, dried with magnesium sulfate, filtered and concentrated under vacuum to afford a solid. The solid was dried overnight under high vacuum to afford [4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid (9a) (1.58 g, 100%, contains a minor amount of isomer) as an off-white solid; EI(+)-HRMS m/z calcd for C17H19ClN2O3 (M+) 334.1084, found 334.1083. Molecular Weight=334.8056; Exact Mass=334.1084

Source