Formaldehyde → Methyl 2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-2-propenoate

HRID 15312Notes

Reaction equation

HRID 15312 reaction equation
[CH3:1][O:2][C:3](=[O:18])[CH2:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[N:13]=2)[N:8]=[CH:7][C:6]=1[F:17].[C:19](=O)([O-])[O-].[K+].[K+].C=O.O>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C1CCCCC1.C(OCC)(=O)C>[F:17][C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:5]=1[C:4](=[CH2:19])[C:3]([O:2][CH3:1])=[O:18])=[N:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 11430Potassium CarbonateHCID 131728169HCID 131728169, compound

Product 1

HCID 57486873Methyl 2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-2-propenoateYield 66%

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]acetate (35.79 g, 143 mmol), benzyltriethylammonium chloride (51.5 g), potassium carbonate (30.4 g) and paraformaldehyde (30.4 g) in cyclohexane (1 litre) was stirred at 80° C. under argon overnight, cooled and shaken with water and ethyl acetate. After separation, the aqueous was re-extracted with ethyl acetate and the combined organic phases dried and evaporated. Chromatography, eluting with 15% ethyl acetate/hexane, provided the product (24.66 g, 66%).

Workup

  1. temperaturecooled
  2. customAfter separation
  3. extractionthe aqueous was re-extracted with ethyl acetate
  4. customthe combined organic phases dried
  5. customevaporated
  6. washChromatography, eluting with 15% ethyl acetate/hexane

Sources & evidence

ORD record
ord-2cb99a55d3544a8c9e5ff12f04ea42ec
Source dataset
uspto-grants-2010_06
Patent number
US07732461B2

Reaction notes

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