Hydrochloric Acid → 6-Chloro-N-(4-fluorophenyl)picolinamide

HRID 429984Notes

Reaction equation

HRID 429984 reaction equation
S(=O)(=O)(O)[OH:2].[Cl:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13](Cl)(Cl)Cl)[N:8]=1.[F:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1.C(N(CC)CC)C.Cl>C1(C)C=CC=CC=1>[F:17][C:18]1[CH:24]=[CH:23][C:21]([NH:22][C:13]([C:9]2[N:8]=[C:7]([Cl:6])[CH:12]=[CH:11][CH:10]=2)=[O:2])=[CH:20][CH:19]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1118Sulfuric Acid2×HCID 8471TriethylamineHCID 97314-FluoroanilineHCID 16004Nitrapyrin

Product 1

HCID 111185076-Chloro-N-(4-fluorophenyl)picolinamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

[A1 is N, A2 is Cl—C, A3, A4 and A5 are CH, R1 is 4-fluorophenyl, X is NR2 and R2 is H in the compound of formula I] Concentrated sulfuric acid (98% by weight, 98.1 g, 1 mol) is added to 2-chloro-6-trichloromethylpyridin (NP, 231 g, 1 mol) over a period of 4 hours. 50% of the sulfuric acid is added at 120° C., 38% at 125° C. and 12% at 130° C. The resulting mixture is stirred for 40 minutes at 130° C. A viscous melted mass is obtained consisting of >90% of a mixture of intermediate IVa1 and Va1 with R1 being H and Hal being Cl. This mass is added to a mixture of 4-fluoroaniline (122.0 g 1.1 mol), triethylamine (202.0 g, 2 mol) and toluene (752 g) at temperatures between 20 and 100° C. within 45 minutes. The resulting reaction mixture is heated to temperatures between 80 and 120° C. and stirred for one hour. The mixture is treated with 500 ml of hydrochloric acid (7.5% by weight) at 80° C. and the phases are separated. The resulting solution of N-(4-fluorophenyl) 2-chloro-pyrid-6-ylinecarboxamide in toluene is used for the preparation of N-(4-fluorophenyl) 2-(3-trifluoromethylphenoxy)-pyrid-6-ylinecarboxamide without further purification.

Workup

  1. customat 125° C.
  2. customat 130° C
  3. customis obtained
  4. customThe resulting reaction mixture
  5. temperatureis heated to temperatures between 80 and 120° C.
  6. stirringstirred for one hour
  7. customthe phases are separated
  8. customThe resulting solution of N-(4-fluorophenyl) 2-chloro-pyrid-6-ylinecarboxamide in toluene is used for the preparation of N-(4-fluorophenyl) 2-(3-trifluoromethylphenoxy)-pyrid-6-ylinecarboxamide without further purification

Sources & evidence

ORD record
ord-0998009648204323842b801c808b021a
Source dataset
uspto-grants-2001_11
Patent number
US06320053B1

Reaction notes

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