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

HRID 429985Notes

Reaction equation

HRID 429985 reaction equation
S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13](Cl)(Cl)Cl)[N:8]=1.C1C(C(/C=C/C2C=CC(F)=CC=2Cl)=[O:24])=CC=C(F)C=1.[F:36][C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=1.C(N(CC)CC)C.Cl>C1(C)C=CC=CC=1>[F:36][C:37]1[CH:43]=[CH:42][C:40]([NH:41][C:13]([C:9]2[N:8]=[C:7]([Cl:6])[CH:12]=[CH:11][CH:10]=2)=[O:24])=[CH:39][CH:38]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 8471TriethylamineHCID 97314-FluoroanilineHCID 16004NitrapyrinHCID 64335047394-01-6

Product 1

HCID 111185076-Chloro-N-(4-fluorophenyl)picolinamideYield 95%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
135 °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, 127.5 g, 1.3 mol) is added to 2-chloro-6-trichloromethylpyridin (NP, 231 g, 1 mol) over a period of three hours at 135° C. The resulting mixture is stirred for three hours at 135° C. A viscous melted mass is obtained consisting of a mixture of intermediate IVa1 and Va1 with R1 being H and Hal being Cl, corresponding to a yield of >95% based on NP. This intermediate product shows a strong infrared band at 1770cm−1 indicating a carbonylchloride group. 13C-NNR (TMS/nitromethane-d3): δ=130.2 (CH-5), 135.3 (CH-3), 143.7 (C-2), 151.4 (CCl-6), 151.5 (CH-4), 164.1 (C═O) ppm. The mass is added to a mixture of 4-fluoroaniline (166.4 g 1.5 mol), triethylamine (202.0 g, 2 mol) and toluene (752 g) at temperatures between 20 and 80° C. over a period of 45 minutes. The resulting reaction mixture is heated to temperatures between 80 and 100° C. and stirred for one hour. The mixture is treated with 500 ml of hydrochloric acid (1.0% 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. customis obtained
  2. additionconsisting of a mixture of intermediate IVa1 and Va1 with R1
  3. customThe resulting reaction mixture
  4. temperatureis heated to temperatures between 80 and 100° C.
  5. stirringstirred for one hour
  6. customthe phases are separated
  7. 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-ca4f2ffe21ce43e9af71c1a4f72632b1
Source dataset
uspto-grants-2001_11
Patent number
US06320053B1

Reaction notes

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