Sodium Carbonate → 4-Methyl-3-(pyridazin-4-yl)benzoic acid

HRID 2188975Notes

Reaction equation

HRID 2188975 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[N:4][CH:3]=1.[CH3:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O>[CH3:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]=1[C:2]1[CH:7]=[CH:6][N:5]=[N:4][CH:3]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 160860864-Methyl-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 178889274-Bromopyridazine

Product 1

HCID 667640094-Methyl-3-(pyridazin-4-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a degassed mixture containing 4-bromopyridazine (0.10 g, 0.63 mmol), 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (0.18 g, 0.69 mmol), sodium carbonate (0.27 g, 2.52 mmol), dioxane (5.2 mL) and water (1.01 mL) was added tetrakis(tiphenylphosphine)palladium(0) (0.02 g, 0.02 mmol) in one portion under a nitrogen atmosphere. The mixture was heated with fast stirring at 95° C. for 4 h, cooled to room temperature and filtered. The filtered solution was acidified to below pH 4 with 1N HCl (5.0 mL). The resultant precipitate was recovered by filtration, washed with water (3×3.0 mL) and air dried. The resultant tan solid was suspended in n-pentane (4 mL), stirred for 20 min, recovered by filtration and air dried to afford 4-methyl-3-(pyridazin-4-yl)benzoic acid as a tan solid which was used without further purification. LCMS: retention time: 1.325 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Sunfire, 5 micron, C18, 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 215 (MH+).

Workup

  1. temperatureThe mixture was heated
  2. temperaturecooled to room temperature
  3. filtrationfiltered
  4. filtrationThe resultant precipitate was recovered by filtration
  5. washwashed with water (3×3.0 mL) and air
  6. customdried
  7. stirringstirred for 20 min
  8. filtrationrecovered by filtration and air
  9. customdried

Sources & evidence

ORD record
ord-94e99d21a0df4a8dab366cb5f7f95a55
Source dataset
uspto-grants-2012_12
Patent number
US08324212B2

Reaction notes

Loading…