Ethyl Acetate → (e)-3-(6-Methoxy-[1,5]naphthyridin-4-yl)-acrylic acid ethyl ester

HRID 1640501Notes

Reaction equation

HRID 1640501 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[N:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][CH:9]=[C:8]2[CH:15]=O.[CH3:17][C:18](=[O:22])[O:19][CH2:20][CH3:21]>C1COCC1.O>[CH2:20]([O:19][C:18](=[O:22])/[CH:17]=[CH:15]/[C:8]1[C:7]2[C:12](=[CH:13][CH:14]=[C:5]([O:4][CH3:3])[N:6]=2)[N:11]=[CH:10][CH:9]=1)[CH3:21]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 665231381,5-Naphthyridine-4-carboxaldehyde, 6-methoxy-

Product 1

HCID 66736305(e)-3-(6-Methoxy-[1,5]naphthyridin-4-yl)-acrylic acid ethyl esterYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Triethylphosphonoacetate (7.3 g, 32.6 mmol) was added to a suspension of a NaH dispersion (1.4 g, 32.5 mmol, 55% in paraffin) in THF (40 mL) at 0° C. The mixture was stirred at 0° C. for 20 min before the dropwise addition of 6-methoxy-[1,5]naphthyridine-4-carbaldehyde (4.0 g, 21.3 mmol; prepared as in WO 2006/032466) in THF. The mixture was stirred at rt for 5 h, diluted with water and EA. The phases were separated and the aq. phase extracted with EA (2 times 50 mL). The combined org. phases were washed with brine, dried over MgSO4 and concentrated. The residue was purified by chromatography on SiO2 (Hex/EA 1:1) to give the desired alkene as a colourless solid (3.0 g, 56% yield).

Workup

  1. customThe phases were separated
  2. extractionthe aq. phase extracted with EA (2 times 50 mL)
  3. washphases were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on SiO2 (Hex/EA 1:1)

Sources & evidence

ORD record
ord-bd630c09c2a449bd99582ee0515eae8f
Source dataset
uspto-grants-2012_02
Patent number
US08114867B2

Reaction notes

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