Acetic Acid → HCID 178424158, compound

HRID 2289949Notes

Reaction equation

HRID 2289949 reaction equation
C(O[C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][C:12]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:23])=[CH:11][C:10]=2[F:24])=[O:5])C.[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH2:31])=[CH:28][CH:27]=1.C(O)(=O)C.Cl>C1(C)C=CC=CC=1>[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH:31][C:4]([C:6]2[CH:7]=[N:8][C:9]3[C:14]([C:15]=2[OH:16])=[CH:13][C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH3:23])=[CH:11][C:10]=3[F:24])=[O:5])=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 660364-ChlorobenzylamineHCID 178469644HCID 178469644, compound

Product 1

HCID 178424158HCID 178424158, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
190 °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. temperatureto cool to rt
  2. extractionis extracted with ethyl acetate (3×25 mL)
  3. dry with materialThe organic layer is dried (MgSO4)
  4. customto crystallize
  5. customRecrystallization from acetic acid/water

Sources & evidence

ORD record
ord-76a098d3d34a4e5b931c564ad5197118
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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