Trifluoroacetic acid → (4-Chloro-benzyl)-(6-chloro-pyridin-2-yl)-amine

HRID 1952105Notes

Reaction equation

HRID 1952105 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[N:6][C:7]=1F.[Cl:18]C1C=CC(C=O)=CC=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C(#N)C>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][NH:9][C:5]2[CH:4]=[CH:3][CH:2]=[C:7]([Cl:18])[N:6]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 77264-ChlorobenzaldehydeHCID 12052TriethylsilaneHCID 57619198(5-Bromo-6-fluoro-pyridin-2-yl)-(4-chloro-benzyl)-amine

Product 1

HCID 57619237(4-Chloro-benzyl)-(6-chloro-pyridin-2-yl)-amine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 6-chloro-pyridin-2-ylamine (537, 5.60 g, 0.0436 mol) in acetonitrile (300 mL) were added 4-chlorobenzaldehyde (40, 6.7 g, 0.048 mol), trifluoroacetic acid (13 mL, 0.17 mol) and triethylsilane (21 mL, 0.13 mol). The reaction was heated to reflux for 4 hours, then concentrated, poured into water, extracted with ethyl acetate, and washed with sodium bicarbonate and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The filtrate was purified with silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give a white solid (538, 6.5 g, 59%). MS (ESI) [M+H+]+=255.1.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 4 hours
  3. concentrationconcentrated
  4. additionpoured into water
  5. extractionextracted with ethyl acetate
  6. washwashed with sodium bicarbonate and brine
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe filtrate was purified with silica gel column chromatography
  11. washeluting with 20% to 100% ethyl acetate in hexane
  12. customto give a white solid (538, 6.5 g, 59%)

Sources & evidence

ORD record
ord-51f47cee66834f28b6d5fd3c1bee90fe
Source dataset
uspto-grants-2013_03
Patent number
US08404700B2

Reaction notes

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