3-(Trifluoromethyl)benzoic acid → HCID 14232986, compound

HRID 580517Notes

Reaction equation

HRID 580517 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([OH:8])=O.S(Cl)(Cl)=O.[NH2:18][C:19]1[CH:20]=[N:21][C:22]2[C:27]([C:28]=1[NH2:29])=[CH:26][CH:25]=[CH:24][CH:23]=2>CN(C)P(N(C)C)(N(C)C)=O.C(#N)C.C(=O)(O)[O-].[Na+]>[NH2:29][C:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[CH:20][C:19]=1[NH:18][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][CH:11]=[C:3]([C:2]([F:1])([F:13])[F:12])[CH:4]=1

Participants

7

Reactant 3

HCID 99633-(Trifluoromethyl)benzoic acidHCID 24386Thionyl ChlorideHCID 15142893,4-Diaminoquinoline

Product 1

HCID 14232986HCID 14232986, compoundYield 98.6%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 12679HexamethylphosphoramideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 500 mg of 3-trifluoromethylbenzoic acid in 6 ml of anhydrous hexamethylphosphoramide (HMPA) and 0.6 ml of anhydrous acetonitrile is added dropwise 305 mg of thionyl chloride at -5°-0° C. under nitrogen. After stirring at the same temperature for 30 minutes, 380 mg of 3,4-diaminoquinoline is added and stirred at 0°-5° C. for 3 hours. The mixture is diluted with ice-water and neutralized with saturated aqueous sodium bicarbonate. The resulting crystals are filtered, washed with water, and dried to give 780 mg of 4-amino-3-(3-trifluoromethylbenzoylamino)quinoline B1 as a crude product. It is suspended in 15 g of polyphosphoric acid and heated at 120° C. for 4 hours with stirring. The mixture is poured into ice-water and neutralized with 1N sodium hydroxide. The resulting solid is filtered, washed with water and dried. It is chromatographed on silica gel with chloroform-methanol (10:1 v/v) as eluent, yielding 350 mg (47%) of C1 as colorless crystals.

Workup

  1. stirringstirred at 0°-5° C. for 3 hours
  2. filtrationThe resulting crystals are filtered
  3. washwashed with water
  4. customdried

Sources & evidence

ORD record
ord-8b117dd8b5d44f5fb8586032ee787adf
Source dataset
uspto-grants-1988_06
Patent number
US04753951

Reaction notes

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