Acetic Acid → 8-chloro-5H-chromeno[2,3-b]pyridin-5-one

HRID 1663410Notes

Reaction equation

HRID 1663410 reaction equation
CN(C)/[CH:3]=[CH:4]/[CH:5]=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:19])[CH2:16][C:17]#[N:18])=[C:11](F)[CH:10]=1.C(O)(=[O:23])C.C(OCC)(=O)C>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]2[C:12]([C:15](=[O:19])[C:16]3[C:17]([O:23]2)=[N:18][CH:3]=[CH:4][CH:5]=3)=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 6383203-(Dimethylamino)acrylaldehydeHCID 247066703-(4-Chloro-2-fluorophenyl)-3-oxopropanenitrile

Product 1

HCID 122026698-chloro-5H-chromeno[2,3-b]pyridin-5-oneYield 10.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (E)-3-(dimethylamino)acrylaldehyde (3.26 g, 32.9 mmol), the product from Step 1 (5.00 g, 25.3 mmol) and acetic acid (7.24 mL, 127 mmol) in DMF (40 mL) was heated to 120° C. for 48 h and cooled to room temperature. Ethyl acetate (400 mL) was added and the mixture washed with saturated NaHCO3 (40 mL), water (40 mL), brine (40 mL), dried (MgSO4) and concentrated. The residue was purified by flash column chromatography (silica, 10-40% ethyl acetate in hexanes) to provide 8-chloro-5H-chromeno[2,3-b]pyridin-5-one (600 mg, 10%). MS (ES+) m/z: 232 (M+H).

Workup

  1. washthe mixture washed with saturated NaHCO3 (40 mL), water (40 mL), brine (40 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (silica, 10-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-ab51d41fdc8e419bb43a9d0862cca3cd
Source dataset
uspto-grants-2011_10
Patent number
US08034940B2

Reaction notes

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