Toluene → Diethyl 2-((2-chloro-5-(trifluoromethyl)phenylamino)methylene)malonate

HRID 1943038Notes

Reaction equation

HRID 1943038 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:3]=1[NH2:4].C(O[CH:16]=[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:18]([O:20][CH2:21][CH3:22])=[O:19])C.C1(C)C=CC=CC=1>CCCCCC>[Cl:1][C:2]1[CH:8]=[CH:7][C:6]([C:9]([F:10])([F:11])[F:12])=[CH:5][C:3]=1[NH:4][CH:16]=[C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:23]([O:25][CH2:26][CH3:27])=[O:24]

Participants

5

Reactant 3

HCID 1140TolueneHCID 6871Diethyl (ethoxymethylene)malonateHCID 8475Benzenamine, 2-chloro-5-(trifluoromethyl)-

Product 1

HCID 2797069Diethyl 2-((2-chloro-5-(trifluoromethyl)phenylamino)methylene)malonate

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
140 °C

Procedure

2-Chloro-5-(trifluoromethyl)aniline (2) (200 g, 1.023 mol), diethyl 2-(ethoxymethylene)malonate (3) (276 g, 1.3 mol) and toluene (100 mL) were combined under a nitrogen atmosphere in a 3-neck, 1-L round bottom flask equipped with Dean-Stark condenser. The solution was heated with stirring to 140° C. and the temperature was maintained for 4 hours (h). The reaction mixture was cooled to 70° C. and hexane (600 mL) was slowly added. The resulting slurry was stirred and allowed to warm to room temperature. The solid was collected by filtration, washed with 10% ethyl acetate in hexane (2×400 mL) and then dried under vacuum to provide the product, diethyl 2-((2-chloro-5-(trifluoromethyl)phenylamino)methylene)malonate (4), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.28 (d, J=13.0 Hz, 1H), 8.63 (d, J=13.0 Hz, 1H), 8.10 (s, 1H), 7.80 (d, J=8.3 Hz, 1H), 7.50 (dd, J=1.5, 8.4 Hz, 1H), 4.24 (q, J=7.1 Hz, 2H), 4.17 (q, J=7.1 Hz,2 H), 1.27 (m, 6H).

Workup

  1. customequipped with Dean-Stark condenser
  2. temperatureThe solution was heated
  3. temperaturethe temperature was maintained for 4 hours (h)
  4. temperatureThe reaction mixture was cooled to 70° C.
  5. stirringThe resulting slurry was stirred
  6. temperatureto warm to room temperature
  7. filtrationThe solid was collected by filtration
  8. washwashed with 10% ethyl acetate in hexane (2×400 mL)
  9. customdried under vacuum

Sources & evidence

ORD record
ord-789d3eeaa22a49679ec0a216b2e73a97
Source dataset
uspto-grants-2013_03
Patent number
US08389727B2

Reaction notes

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