Pyridine → HCID 57606115, compound

HRID 572266Notes

Reaction equation

HRID 572266 reaction equation
[N:1]1([C:7]([C:9]2[S:13][C:12]([CH:14]=O)=[CH:11][CH:10]=2)=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:16]1C=CC=CC=1.Cl.NO>CCO>[N:1]1([C:7]([C:9]2[S:13][C:12]([C:14]#[N:16])=[CH:11][CH:10]=2)=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 443297Hydroxyamine hydrochlorideHCID 57606128HCID 57606128, compound

Product 1

HCID 57606115HCID 57606115, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
145 °C

Procedure

A solution of 5-(Piperidine-1-carbonyl)-thiophene-2-carbaldehyde (Preparative Example 17, 2.23 g, 10 mmol) in EtOH (50 mL) was treated with pyridine (971 μL, 12 mmol, 1.2 eq) followed by hydroxylamine hydrochloride (833 mg, 12 mmol, 1.2 eq) and heated at reflux for 2 hr then evaporated in vacuo. The crude intermediate oxime was then dissolved in acetic anhydride and heated at 145° C. for 16 hr then evaporated in vacuo to a small volume which was partitioned between EtOAc (50 mL) and water (200 mL). The organic layer was further washed with a brine solution (50 mL), dried over MgSO4, filtered, evaporated in vacuo and the residue chromatographed on silica gel with EtOAc/hexanes (30 then 50%) as eluant to afford product as a yellow-tinted oil (1.43 g, 65%). 1H NMR (CDCl3) 1.65-1.76 (m, 6H), 3.64 (br s, 4H), 7.23 (d, J=4.0, 1H), 7.56 (d, J=4.0, 1H). 13C NMR 24.5, 26.2, 44.3 (br), 48.5 (br), 111.9, 113.7, 128.0, 137.0, 144.7, 161.3. LC/MS 5.09 min, [M+1]+ 221.

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 hr
  3. customthen evaporated in vacuo
  4. dissolutionThe crude intermediate oxime was then dissolved in acetic anhydride
  5. customthen evaporated in vacuo to a small volume which
  6. customwas partitioned between EtOAc (50 mL) and water (200 mL)
  7. washThe organic layer was further washed with a brine solution (50 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customthe residue chromatographed on silica gel with EtOAc/hexanes (30

Sources & evidence

ORD record
ord-85319d80994a46cfb907a3e1d89a19f4
Source dataset
uspto-grants-2015_05
Patent number
US09029397B2

Reaction notes

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