Methyl acetoacetate → Methyl 4-(4-chloro-2-fluorophenyl)-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylate

HRID 734663Notes

Reaction equation

HRID 734663 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([F:10])[CH:3]=1.[CH3:11][C:12]1(C)[O:17]C(=O)CC(=O)O1.[C:21]([O:27][CH3:28])(=[O:26])[CH2:22][C:23]([CH3:25])=O.C([O-])(=O)C.[NH4+:33].C([O-])([O-])=O.[K+].[K+]>C(O)(=O)C.CCOC(C)=O.O>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]2[CH2:11][C:12](=[O:17])[NH:33][C:23]([CH3:25])=[C:22]2[C:21]([O:27][CH3:28])=[O:26])=[C:4]([F:10])[CH:3]=1

Participants

9

Reactant 5

HCID 7757Methyl acetoacetateHCID 11430Potassium CarbonateHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 517165Ammonium AcetateHCID 27249084-Chloro-2-fluorobenzaldehyde

Product 1

HCID 68826805Methyl 4-(4-chloro-2-fluorophenyl)-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylateYield 27%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Chloro-2-fluorobenzaldehyde (1.00 g, 6.30 mmol, 1.00 equiv), 2,2-dimethyl-1,3-dioxane-4,6-dione (907 mg, 6.30 mmol, 1.00 equiv), methyl acetoacetate (0.679 mL, 6.30 mmol, 1.00 equiv), and ammonium acetate (0.512 g, 6.60 mmol, 1.05 equiv) were dissolved in acetic acid (7.0 mL) and heated to reflux for 2 hours. The reaction mixture was cooled to room temperature, neutralized with solid K2CO3, and diluted with EtOAc and water. The phases were separated, and the organic phase was washed with satd. NaCl. The organic phase was dried over Na2SO4, filtered and concentrated to a yellow residue. Recrystallization (CH2Cl2/hexanes) provided 503 mg (27%) of the product as a pale yellow solid. MS (ES+) m/e 298 [M+H]+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 hours
  3. customThe phases were separated
  4. washthe organic phase was washed with satd
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a yellow residue
  8. customRecrystallization (CH2Cl2/hexanes)

Sources & evidence

ORD record
ord-0b2d46c3b3bc43a8bf10760d7caf98ac
Source dataset
uspto-grants-2009_09
Patent number
US07592357B2

Reaction notes

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