4-(Trifluoromethyl)aniline → 3-Methylsulfanyl-5-trifluoromethyl-1,3-dihydro-indol-2-one

HRID 1576952Notes

Reaction equation

HRID 1576952 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.C(=O)=O.[CH:15]([OH:18])(C)[CH3:16].ClOC(C)(C)C.CC[C:27](OCC)=[S:28]>C(Cl)Cl.C(N(CC)CC)C>[CH3:27][S:28][CH:16]1[C:7]2[C:2](=[CH:3][CH:4]=[C:5]([C:8]([F:9])([F:10])[F:11])[CH:6]=2)[NH:1][C:15]1=[O:18]

Participants

7

Reactant 4

HCID 99644-(Trifluoromethyl)anilineHCID 521297Tert-Butyl hypochloriteHCID 12284386Ethyl methylthioacetateHCID 86586944Isopropanol carbon dioxide

Product 1

HCID 123514913-Methylsulfanyl-5-trifluoromethyl-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent5×HCID 8471TriethylamineSolvent

Conditions

Temperature
15 °C

Procedure

To a solution of 30.8 of p-aminobenzotrifluoride predissolved in 450 ml. of methylene chloride, cooled to -58°C. (dry ice/isopropanol bath), and under an atmosphere of nitrogen, is added dropwise a solution of 21.1 ml. of t-butyl hypochlorite in 30 ml. of methylene chloride over 30 minutes while the reaction miture is maintained at -55° to 58°C. After the reaction mixture is stirred an additional five minutes, a solution of 25.6 g. of ethyl methylthioacetate in 30 ml. of methylene chloride is added dropwise over a period of 20 minutes while the reaction mixture is maintained at -55° to -58°C. The reaction mixture is stirred one hour at -55° to -65°C. and 60 ml. of methylene chloride is added to facilitate stirring. A solution of 25 ml. of triethylamine in 25 ml. of methylene chloride is added dropwise over a period of 10 minutes while the reaction mixture is maintained at -50°C. to -60°C. After an additional three minutes stirring, the cold bath is removed and the reaction mixture allowed to warm to 15°C. over a period of two hours; then 100 ml. of water is added. The organic phase is separated and concentrated in vacuo to an oil which is then dissolved in 100 ml. of ether. The ethereal solution is treated with 50 ml. of 2N hydrochloric acid, and the mixture is stirred overnight at room temperature. The phases are separated and the product is obtained in two portions by crystallization with cooling, followed by concentration of the mother liquors to a solid in vacuo. Recrystallization from ether/pentane gives 3-methylthio-5 -trifluoromethyl-2-indolinone, m.p. 136°-138°C.

Workup

  1. additionunder an atmosphere of nitrogen, is added dropwise a solution of 21.1 ml
  2. temperatureis maintained at -55° to -58°C
  3. stirringThe reaction mixture is stirred one hour at -55° to -65°C.
  4. stirringto facilitate stirring
  5. temperatureis maintained at -50°C. to -60°C
  6. stirringAfter an additional three minutes stirring
  7. customthe cold bath is removed
  8. additionof water is added
  9. customThe organic phase is separated
  10. concentrationconcentrated in vacuo to an oil which
  11. dissolutionis then dissolved in 100 ml
  12. additionThe ethereal solution is treated with 50 ml
  13. stirringof 2N hydrochloric acid, and the mixture is stirred overnight at room temperature
  14. customThe phases are separated
  15. customthe product is obtained in two portions by crystallization
  16. temperaturewith cooling
  17. customRecrystallization from ether/pentane

Sources & evidence

ORD record
ord-12acee076e4442a0b79a4c2ec99e9cd6
Source dataset
uspto-grants-1976_09
Patent number
US03983242

Reaction notes

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