Toluene → HCID 178471786, compound

HRID 505297Notes

Reaction equation

HRID 505297 reaction equation
F[C:2]1[C:3]([CH:8]=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:10]([O:12][C:13](=[O:25])[CH2:14][C@H:15]1[CH2:20][CH2:19][C@H:18]([CH2:21][NH:22][CH2:23][CH3:24])[CH2:17][CH2:16]1)[CH3:11].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>O>[CH2:23]([N:22]([CH2:21][C@H:18]1[CH2:19][CH2:20][C@H:15]([CH2:14][C:13]([O:12][CH2:10][CH3:11])=[O:25])[CH2:16][CH2:17]1)[C:2]1[C:3]([CH:8]=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1)[CH3:24]

Participants

6

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 113440173-Fluoro-2-pyridinecarboxaldehydeHCID 178464368HCID 178464368, compound

Product 1

HCID 178471786HCID 178471786, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 3-fluoropyridine-2-carbaldehyde (122.7 mg, 0.981 mmol), ethyl{trans-4-[(ethylamino)methyl]cyclohexyl}acetate (202.7 mg, 0.892 mmol), potassium carbonate (369.7 mg, 2.67 mmol) and dry toluene (13 mL) was heated at reflux under N2 overnight. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-50% EtOAc in hexanes gradient) to afford ethyl (trans-4-{[ethyl(2-formylpyridin-3-yl)amino]methyl}cyclohexyl)acetate as a yellow oil. Rf=0.79 (50% EtOAc/hexanes). LCMS calc.=333.2; found=333.3 (M+1)+. 1H NMR (600 MHz, CDCl3): δ 10.13 (s, 1 H); 8.29 (d, J=4.1 Hz, 1 H); 7.41 (d, J=8.5 Hz, 1 H); 7.29 (dd, J=4.1, 8.4 Hz, 1 H); 4.08 (q, J=7.1 Hz, 2 H); 3.26 (q, J=7.0 Hz, 2 H); 3.05 (d, J=7.1 Hz, 2 H); 2.12 (d, J=6.9 Hz, 2 H); 1.71 (m, 4 H); 1.66 (m, 1 H); 1.41 (m, 1 H); 1.22-1.20 (t, J=7.1 Hz, 3 H); 1.06 (t, J=7.1 Hz, 3 H); 0.91-0.82 (m, 4 H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux under N2 overnight
  3. extractionextracted with EtOAc (3×20 mL)
  4. dry with materialThe combined extracts were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto give the crude product
  7. customThis was purified by flash chromatography (Si, 12×160 mm, 0-50% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-9296d03c53984a43b5de8ccd5dfed3bf
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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