Hexane → 1-(4-fluoro-3-methylphenyl)-5-(trifluoromethyl)-1H-tetrazole

HRID 1006346Notes

Reaction equation

HRID 1006346 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]([CH3:13])[CH:7]=1)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCCCCC.[N-:41]=[N+:42]=[N-:43].[Na+]>ClC(Cl)(Cl)Cl.C(O)(=O)C>[F:12][C:9]1[CH:10]=[CH:11][C:6]([N:5]2[C:3]([C:2]([F:15])([F:14])[F:1])=[N:43][N:42]=[N:41]2)=[CH:7][C:8]=1[CH3:13]

Participants

7

Reactant 4

HCID 8058HexaneHCID 11776Triphenylphosphine3×HCID 33557Sodium AzideHCID 226747632,2,2-trifluoro-N-(4-fluoro-3-methylphenyl)acetamide

Product 1

HCID 226746621-(4-fluoro-3-methylphenyl)-5-(trifluoromethyl)-1H-tetrazoleYield 95.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2,2,2-trifluoro-N-(4-fluoro-3-methylphenyl)acetamide (14.3 g) and triphenylphosphine (19.5 g) in tetrachloromethane (140 ml) was stirred for 17 hours at 100° C. An additional triphenylphosphine (5 g) was added to the mixture and the whole was stirred for 5 hours and finally triphenylphosphine (5 g) was added to the mixture, and the whole was stirred further for 15 hours at 100° C. After being cooled to room temperature hexane was added to the reaction mixture and the whole was stirred for 0.5 hour under ice-cooling. The resulting precipitate was removed by filtration and washed with hexane. The combined filtrate and washing were evaporated under reduced pressure below 20° C. A mixture of the syrup obtained and sodium azide (10.6 g) in acetic acid (100 ml) was stirred at room temperature for 7 hours, followed by at 70° C. for 17 hours. After being cooled to room temperature, the mixture was poured into ice-water, and extracted with dichloromethane. The organic layer was separated, dried over magnesium sulfate, and evaporated under reduced pressure. The syrup was purified by column chromatography on silica gel using a mixed solvent of hexane and ethyl acetate (100:1-5:1). The fractions containing the objective compound were collected to give 1-(4-fluoro-3-methylphenyl)-5-(trifluoromethyl)-1H-tetrazole (15.2 g) as a syrup.

Workup

  1. stirringthe whole was stirred for 5 hours
  2. stirringthe whole was stirred further for 15 hours at 100° C
  3. additionwas added to the reaction mixture
  4. stirringthe whole was stirred for 0.5 hour under ice-
  5. temperaturecooling
  6. customThe resulting precipitate was removed by filtration
  7. washwashed with hexane
  8. washThe combined filtrate and washing
  9. customwere evaporated under reduced pressure below 20° C
  10. additionA mixture of the syrup
  11. customobtained
  12. waitfollowed by at 70° C. for 17 hours
  13. temperatureAfter being cooled to room temperature
  14. extractionextracted with dichloromethane
  15. customThe organic layer was separated
  16. dry with materialdried over magnesium sulfate
  17. customevaporated under reduced pressure
  18. customThe syrup was purified by column chromatography on silica gel using a mixed solvent of hexane and ethyl acetate (100:1-5:1)
  19. additionThe fractions containing the objective compound
  20. customwere collected

Sources & evidence

ORD record
ord-f10ffa9fddbc4fb5948e3ba963e93818
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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