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

HRID 2199100Notes

Reaction equation

HRID 2199100 reaction equation
C[O:2][C:3](=[O:24])[CH2:4][C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([O:12][C:13]2[N:14]=[N:15][C:16]([Cl:22])=[C:17]([CH:19]([CH3:21])[CH3:20])[CH:18]=2)=[C:7]([CH3:23])[CH:6]=1.[OH-].[Na+]>CO>[Cl:22][C:16]1[N:15]=[N:14][C:13]([O:12][C:8]2[C:9]([CH3:11])=[CH:10][C:5]([CH2:4][C:3]([OH:24])=[O:2])=[CH:6][C:7]=2[CH3:23])=[CH:18][C:17]=1[CH:19]([CH3:21])[CH3:20]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59834457[4-(6-Chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester

Product 1

HCID 59834543[4-(6-Chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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

Workup

  1. customat room temperature
  2. concentrationAt this time, the reaction mixture was concentrated under vacuum
  3. additionThe resulting solid was diluted with water (200 mL)
  4. extractionextracted with ethyl acetate (200 mL)
  5. additionThe water layer was acidified to pH=4 by the addition of a 1N aqueous hydrochloric acid solution
  6. extractionwas extracted with ethyl acetate (2×200 mL)
  7. washwashed with a saturated aqueous sodium chloride solution
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customto afford a solid
  12. customThe solid was dried overnight under high vacuum

Sources & evidence

ORD record
ord-5f22e7a4100847a0b6eb6f2dd78f20b0
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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