Trifluoroacetic acid → 6-Ethoxy-5-(trifluoromethyl)pyridin-2-amine

HRID 545085Notes

Reaction equation

HRID 545085 reaction equation
COC1C=CC(C[N:8]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[C:20]([O:28][CH2:29][CH3:30])[N:19]=2)CC2C=CC(OC)=CC=2)=CC=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CCOC(C)=O>[NH2:8][C:18]1[N:19]=[C:20]([O:28][CH2:29][CH3:30])[C:21]([C:24]([F:27])([F:25])[F:26])=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 67190754N,N-Bis-(4-methoxybenzyl)-(6-ethoxy-5-trifluoromethylpyridine-2-yl)amine

Product 1

HCID 574468476-Ethoxy-5-(trifluoromethyl)pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Stir a mixture of N,N-Bis-(4-methoxybenzyl)-(6-ethoxy-5-trifluoromethylpyridine-2-yl)amine (630 mg, 1.41 mmol) and TFA (5 mL) at 60° C. for 18 hours. At this time, TLC (80% Hexanes/EtOAc) reveals no remaining starting material. Cool the reaction mixture to room temperature, and remove excess TFA under vacuum to give a greenish-brown oil. Add EtOAc (20 mL) and sat. aqueous NaHCO3 (20 mL), and stir the mixture until the entire solid dissolves. Separate the layers, and extract the aqueous layer with another 10 mL EtOAc. Dry the combined EtOAc extracts (Na2SO4), filter, and evaporate to give a brown oil. Purification by column chromatography affords the title product as pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.54 (d, 1H, J=8.4 Hz), 6.0 (d, 1H, J=8.4 Hz), 4.56 (bs, 2H), 4.37 (q, 2H, J=6.8 and 7.2 Hz), 1.36 (t, 3H, J=7.2 and 6.8 Hz). Mass spec. (207.13, M+H).

Workup

  1. customremove excess TFA under vacuum
  2. customto give a greenish-brown oil
  3. dissolutiondissolves
  4. customSeparate the layers
  5. extractionextract the aqueous layer with another 10 mL EtOAc
  6. dry with materialDry the combined EtOAc
  7. filtrationfilter
  8. customevaporate
  9. customto give a brown oil
  10. customPurification by column chromatography

Sources & evidence

ORD record
ord-e2c10d39f5e44cf59154fe22896915d6
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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