Iodine → 4-Chloro-8-(trifluoromethyl)quinoline

HRID 1277517Notes

Reaction equation

HRID 1277517 reaction equation
II.P(Cl)(Cl)([Cl:5])=O.[F:8][C:9]([F:23])([F:22])[C:10]1[CH:21]=[CH:20][CH:19]=[CH:18][C:11]=1[NH:12][CH2:13][CH2:14][C:15](O)=O.S(=O)(O)[O-].[Na+]>O>[Cl:5][C:15]1[C:18]2[C:11](=[C:10]([C:9]([F:23])([F:22])[F:8])[CH:21]=[CH:20][CH:19]=2)[N:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 807IodineHCID 24813Phosphorus oxychlorideHCID 23454281N-[2-(Trifluoromethyl)phenyl]-β-alanineHCID 23665763Sodium Bisulfite

Product 1

HCID 902624-Chloro-8-(trifluoromethyl)quinoline

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

13.75 g of monosublimated iodine were added at 0° to 5° C. to75 ml of phosphorus oxychloride and the mixture was heated over 30 minutes to 93°-95° C. and was held at 93°-95° C. for about 30 minutes. Then, 50 g of the product of Step A were added over 6 minutes in fractions of 1.250 g to the mixture and then the mixture was held at 93°-95° C. for 30 minutes. After cooling to 70°±5° C., the mixture was added over about 30 minutes toa stirred solution of 11 g of sodium bisulfite in 875 ml of water held at 40° to 45° C. The mixture was cooled over 30 minutes to 15°-20° C. to obtain a gummy suspension which was vacuum filtered washed and dried. The product was crystallized from methanol to obtain 36.9 g of 4-chloro-8-trifluoromethyl-quinoline with a 98% purity.

Workup

  1. temperaturethe mixture was heated over 30 minutes to 93°-95° C.
  2. waitthe mixture was held at 93°-95° C. for 30 minutes
  3. temperatureAfter cooling to 70°±5° C.
  4. additionthe mixture was added over about 30 minutes toa
  5. customheld at 40° to 45° C
  6. temperatureThe mixture was cooled over 30 minutes to 15°-20° C.
  7. customto obtain a gummy suspension which
  8. filtrationfiltered
  9. washwashed
  10. customdried
  11. customThe product was crystallized from methanol

Sources & evidence

ORD record
ord-218d8ca85ad6490b808505bd334e121b
Source dataset
uspto-grants-1981_07
Patent number
US04277607

Reaction notes

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