Hydrochloric Acid → 5-Methyl-2-nitro-4-(trifluoromethyl)aniline

HRID 418136Notes

Reaction equation

HRID 418136 reaction equation
[C:1]([O-])(C)(C)C.[K+].C(OCC)(=O)CC(OCC)=O.Cl[C:19]1[C:20]([C:29]([F:32])([F:31])[F:30])=[CH:21][C:22]([N+:26]([O-:28])=[O:27])=[C:23]([NH2:25])[CH:24]=1.[OH-].[K+].Cl>CS(C)=O.O>[CH3:1][C:19]1[C:20]([C:29]([F:32])([F:31])[F:30])=[CH:21][C:22]([N+:26]([O-:28])=[O:27])=[C:23]([NH2:25])[CH:24]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 14797Potassium HydroxideHCID 27738135-Chloro-2-nitro-4-(trifluoromethyl)anilineHCID 23665647Potassium tert-butoxide

Product 1

HCID 534083075-Methyl-2-nitro-4-(trifluoromethyl)anilineYield 91%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

Under argon atmosphere, a suspension of potassium tert-butanolate (71.6 g, 625 mmol) in DMSO (150 mL) was placed in a 1.5 L flask, fitted with a mechanical stirrer. Then diethyl malonate (97.9 mL, 625 mmol) was added drop wise at 20-30° C. under ice bath cooling. To the thick white suspension was the added solid commercially available 5-chloro-2-nitro-4-trifluoromethyl-phenylamine [CAS-No. 35375-74-7] (60.14 g, 250 mmol) in one portion, the mixture was diluted with DMSO (100 mL) and the red solution warmed up to 60° C. and stirred for 20 h at 60° C. The mixture was cooled to 23° C. and a solution of potassium hydroxide (85%, 65.24 g, 1 mol) in water (100 mL) was added drop wise. The mixture was then heated to 100° C. and stirred for further 4 h. The mixture was cooled to 23° C., diluted with water (ca. 1000 mL), acidified with 37% HCl 3 to pH 3, and extracted three times with tert-butyl methyl ether (TBME) The organic layers were washed with brine, dried over MgSO4 and evaporated to give a brown solid, which was triturated with hot heptane, filtered off and washed with heptane to give the title compound as a brown solid (50.0 g, 91%), which was used without further purification. MS (ISN) 218.9 [M−H].

Workup

  1. customwas placed in a 1.5 L flask
  2. customfitted with a mechanical stirrer
  3. temperaturecooling
  4. temperatureThe mixture was cooled to 23° C.
  5. temperatureThe mixture was then heated to 100° C.
  6. stirringstirred for further 4 h
  7. temperatureThe mixture was cooled to 23° C.
  8. extractionextracted three times with tert-butyl methyl ether (TBME) The organic layers
  9. washwere washed with brine
  10. dry with materialdried over MgSO4
  11. customevaporated
  12. customto give a brown solid, which
  13. customwas triturated with hot heptane
  14. filtrationfiltered off
  15. washwashed with heptane

Sources & evidence

ORD record
ord-1e1bc6d581b348e2823eada44a892500
Source dataset
uspto-grants-2012_01
Patent number
US08093263B2

Reaction notes

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