2-Pyridinecarboxaldehyde → HCID 22939391, compound

HRID 1774012Notes

Reaction equation

HRID 1774012 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]=O.[C:9]([CH2:14][CH:15]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:11][CH2:12][CH3:13])=[O:10]>C1(C)C=CC=CC=1>[CH2:12]([O:11][C:9](=[O:10])[CH:14]([CH3:15])[CH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)[CH3:13]

Participants

4

Reactant 2

HCID 142732-PyridinecarboxaldehydeHCID 12607919Ethyl 3-(triphenyl-lambda~5~-phosphanylidene)propanoate

Product 1

HCID 22939391HCID 22939391, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 2-pyridinecarboxaldehyde (0.96 mL, 10 mmol, 1.0 eq.) in toluene (17 mL) was added a solution of (carbethoxyethylidene)triphenylphosphorane (6.50 g, 16.1 mmol, 1.6 eq.) in toluene (24 mL). The resulting mixture was stirred at 80° C. for 18 hours. The solvent was removed in vacuo. The residue was suspended in a minimum amount of water and DCM was added. The product was extracted with 5% HCl soln. The aq. phase was cooled down to 0° C. and was basified with solid K2CO3. The product was then extracted with DCM (2×) and the comb. org. layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 45 fractions of 45 mL, Heptane 100% to Heptane+25% AcOEt). To a solution of the resulting α,β-unsaturated ester in THF (21 mL) under N2, palladium on activated carbon (10 wt. %, 33 mg) was added. The flask was carefully evacuated and refilled with H2 (3×). The black suspension was stirred at 45° C. under an H2-atmosphere for 18 hours. The black suspension was filtered through Celite. The Celite was rinsed with THF. The filtrate was concentrated in vacuo. The residue was purified by flashmaster (column: 25 g, flow: 30 mL/min, 30 fractions of 30 mL, Heptane 100% to Heptane+AcOEt 30%) to yield (±)-2-methyl-3-pyridin-2-yl-propionic acid ethyl ester as a colorless oil.

Workup

  1. customThe solvent was removed in vacuo
  2. additionwas added
  3. extractionThe product was extracted with 5% HCl soln
  4. temperatureThe aq. phase was cooled down to 0° C.
  5. extractionThe product was then extracted with DCM (2×)
  6. dry with materiallayers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 45 fractions of 45 mL, Heptane 100% to Heptane+25% AcOEt)
  10. additionTo a solution of the resulting α,β-unsaturated ester in THF (21 mL) under N2, palladium on activated carbon (10 wt. %, 33 mg) was added
  11. customThe flask was carefully evacuated
  12. additionrefilled with H2 (3×)
  13. stirringThe black suspension was stirred at 45° C. under an H2-atmosphere for 18 hours
  14. filtrationThe black suspension was filtered through Celite
  15. washThe Celite was rinsed with THF
  16. concentrationThe filtrate was concentrated in vacuo
  17. customThe residue was purified by flashmaster (column: 25 g, flow: 30 mL/min, 30 fractions of 30 mL, Heptane 100% to Heptane+AcOEt 30%)

Sources & evidence

ORD record
ord-2278b053d6ed4a67a6798e0ab79b892b
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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