4-Fluoro-3-(trifluoromethyl)aniline → HCID 57501605, compound

HRID 1907833Notes

Reaction equation

HRID 1907833 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.C(N(C(C)C)CC)(C)C.[F:19][C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][C:21]=1[C:27]([F:30])([F:29])[F:28]>O1CCOCC1.CCOCC.O>[Cl:1][C:2]1[N:3]=[C:4]([NH:24][C:23]2[CH:25]=[CH:26][C:20]([F:19])=[C:21]([C:27]([F:30])([F:28])[F:29])[CH:22]=2)[CH:5]=[C:6]([Cl:8])[N:7]=1.[Cl:9][C:4]1[CH:5]=[C:6]([Cl:8])[N:7]=[C:2]([NH:24][C:23]2[CH:25]=[CH:26][C:20]([F:19])=[C:21]([C:27]([F:30])([F:28])[F:29])[CH:22]=2)[N:3]=1

Participants

8

Reactant 3

HCID 753774-Fluoro-3-(trifluoromethyl)anilineHCID 773782,4,6-TrichloropyrimidineHCID 81531Diisopropylethylamine

Product 2

HCID 57501605HCID 57501605, compoundYield 63%HCID 57501606HCID 57501606, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

To a stirred solution of commercially available 2,4,6-trichloropyrimidine (XXI) (10.0 g, 52.5 mmol) and diisopropylethylamine (7.7 g, 52.5 mmol) in dioxane (50 mL) under inert atmosphere was added a solution of 4-fluoro-3-trifluoromethylaniline (XX) (9.70 g, 52.5 mmol) in dioxane (150 mL) and then the mixture was heated to 80° C. and stirred for 12 h. The mixture was cooled to ambient temperature and diluted with ether (200 mL) and water (50 mL). The organic phase was separated, successively rinsed with 1N aqueous hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate and filtered. Removal of the volatiles under vacuum on a rotary evaporator gave a gummy solid. This solid was purified by flash column chromatography (silica gel, hexanes/ethyl acetate) to give two isomeric products (2,6-dichloropyrimidin-4-yl)-(4-fluoro-3-trifluoromethylphenyl)amine (XXII) (11.2 g, 63% yield) and (4,6-dichloropyrimidin-2-yl)-(4-fluoro-3-trifluoromethylphenyl)amine (XXIII) (5.2 g 29% yield). Compound XXII: m.p. 129-130° C.; 1H NMR (CDCl3) δ 7.60 (m, 2H), 7.28 (m, 1H), 6.45 (s, 1H); GCMS (m/z) 325 (M−1+); Compound XXIII: m.p.=102-104° C.; 1H NMR (CDCl3) δ 7.86 (dd, J=6.6, 2.7 Hz, 1H), 7.76 (m, 1H), 7.20 (t, J=6.6 Hz,1H), 6.84 (s, 1H); GCMS (m/z) 325 (M−1+)

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customThe organic phase was separated
  3. washsuccessively rinsed with 1N aqueous hydrochloric acid and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customRemoval of the volatiles under vacuum
  7. customon a rotary evaporator
  8. customgave a gummy solid
  9. customThis solid was purified by flash column chromatography (silica gel, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-5cf3c554d1534c5c9a6640447d4d5744
Source dataset
uspto-grants-2013_12
Patent number
US08598182B2

Reaction notes

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