Glycerol → Quinoline, 7,8-Difluoro-

HRID 2174202Notes

Reaction equation

HRID 2174202 reaction equation
S(=O)(=O)(O)O.[F:6][C:7]1[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:8]=1[NH2:9].O[CH2:16][CH:17]([CH2:19]O)O>[I-].[Na+]>[F:14][C:13]1[C:7]([F:6])=[C:8]2[C:10]([CH:16]=[CH:17][CH:19]=[N:9]2)=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 753GlycerolHCID 1118Sulfuric AcidHCID 782782,3-Difluoroaniline

Product 1

HCID 3025799Quinoline, 7,8-Difluoro-Yield 91%

Reagents, catalysts & solvents 1

HCID 5238Sodium IodideCatalyst

Conditions

Temperature
0 °C

Procedure

607.7 g (49.57 mol) of 80% sulfuric acid were placed in a 3 L eggplant flask containing a stirrer followed by cooling to 0° C. 160.0 g (1.24 mol) of 2,3-difluoroaniline were gradually added thereto. Following completion of addition, the reaction mixture was stirred for 1 hour at room temperature. 1.85 g (12.3 mmol) of sodium iodide were then added thereto followed by heating with an oil bath at 150° C. When the liquid temperature reached 150° C., 125.5 g (1.36 mol) of glycerin were dropped therein over the course of 1 hour. Following completion of dropping, the reaction mixture was stirred for 1 hour at 150° C. Next, the temperature of the oil bath was raised to 180° C. Water was distilled off over the course of 2 hours using a distillation apparatus. After confirming elimination of the raw materials, the reaction mixture was neutralized with 10 N aqueous sodium hydroxide solution while cooling in an ice water bath (internal temperature: 60° C. to 70° C.). Following neutralization, the reaction mixture was extracted with ethyl acetate before the internal temperature returned to room temperature, and then the extract was dried with magnesium sulfate, filtered, and concentrated. The resulting crude product was purified by silica gel column chromatography (n-hexane:ethyl acetate) to obtain 185.5 g (91%) of 7,8-difluoroquinoline in the form of a light brown solid.

Workup

  1. additioncontaining a stirrer
  2. additioncompletion of addition
  3. temperatureby heating with an oil bath at 150° C
  4. customreached 150° C.
  5. customover the course of 1 hour
  6. stirringthe reaction mixture was stirred for 1 hour at 150° C
  7. temperatureNext, the temperature of the oil bath was raised to 180° C
  8. distillationWater was distilled off over the course of 2 hours
  9. temperaturewhile cooling in an ice water bath (internal temperature: 60° C. to 70° C.)
  10. extractionthe reaction mixture was extracted with ethyl acetate before the internal temperature
  11. customreturned to room temperature
  12. dry with materialthe extract was dried with magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe resulting crude product was purified by silica gel column chromatography (n-hexane:ethyl acetate)

Sources & evidence

ORD record
ord-e470d840a22f4e0f9ca2aa673d431fa3
Source dataset
uspto-grants-2015_06
Patent number
US09060517B2

Reaction notes

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