2-Methylphenyl boronic acid → HCID 178469644, compound

HRID 2289948Notes

Reaction equation

HRID 2289948 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][C:12](I)=[CH:11][C:10]=2[F:18])=[O:5])[CH3:2].[C:19]1([CH3:28])[C:20](B(O)O)=[CH:21][CH:22]=[CH:23][CH:24]=1.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>CN(C=O)C.O>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][C:12]([C:24]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH3:28])=[CH:11][C:10]=2[F:18])=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 27332672-Methylphenyl boronic acidHCID 17749109Barium hydroxide, octahydrateHCID 178469647HCID 178469647, compound

Product 1

HCID 178469644HCID 178469644, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

6-Iodo-8-fluoro-4-hydroxy-3-quinolinecarboxylic acid ethyl ester (903 mg) from Example No. 5 and o-tolueneboronic acid (374 mg) are dissolved in DMF (50 mL) and at 50° C. a solution of barium hydroxide octahydrate (1.18 g) in water (5 mL) is added followed by palladium tetrakistriphenylphosphine (58 mg). The mixture is heated at 80° C. for 20 h, allowed to cool to rt, poured into water (200 mL), and extracted with ethyl acetate (3×100 mL). The organic layer is washed with brine (25 mL), dried (MgSO4), and concentrated. The solid is then triturated with MTBE, and filtered to afford 382 mg of 6-(2-methylphenyl)-8-fluoro-4-hydroxy-3-quinoline-carboxylic acid ethyl ester. The crude ester is mixed with 4-chlorobenzylamine (380 mg) and is heated to 190° C. for 1 h. The mixture is diluted with toluene (4 mL), allowed to cool to rt, poured into a mixture of 50% acetic acid (10 mL) and 1 N hydrochloric acid (25 mL), and is extracted with ethyl acetate (3×25 mL). The organic layer is dried (MgSO4) and allowed to crystallize. Recrystallization from acetic acid/water affords 166 mg of the title compound.

Workup

  1. additionis added
  2. temperatureto cool to rt
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. washThe organic layer is washed with brine (25 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe solid is then triturated with MTBE
  8. filtrationfiltered

Sources & evidence

ORD record
ord-64bbc90262374e5d9c4f86f89c70d0ca
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

Loading…