Potassium Carbonate → 2-Oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridine-4-carboxylic acid ethyl ester

HRID 500537Notes

Reaction equation

HRID 500537 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][NH:9][C:8](=[O:12])[CH:7]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].C(N(C(C)C)CC)(C)C.[CH3:28][Si:29]([CH3:36])([CH3:35])[CH2:30][CH2:31][O:32][CH2:33]Cl>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][N:9]([CH2:33][O:32][CH2:31][CH2:30][Si:29]([CH3:36])([CH3:35])[CH3:28])[C:8](=[O:12])[CH:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 81531Diisopropylethylamine2×HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 22625086Ethyl 2-oxo-1,2-dihydropyridine-4-carboxylate

Product 1

HCID 248517012-Oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridine-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The title compound of example 18.1 (32 g, 191 mmol) and potassium carbonate (132 g, 957 mmol) were stirred in dimethylformamide (350 mL) at room temperature. Diisopropylethylamine (10 mL, 57 mmol) was added via a syringe, followed by 2-(trimethylsilyl)ethoxymethyl chloride (44.0 mL, 249 mmol). The reaction was stirred at room temperature and diisopropylethylamine (56.6 mL, 325 mmol) was added over 5 hours via a pressure equalized addition funnel. The reaction was then stirred overnight at room temperature. When TLC analysis showed that the reaction was complete the reaction mixture was diluted with ethyl acetate and washed four times with water and once with brine. The organic phase was dried over magnesium sulfate, filtered and concentrated. The residue was chromatographed on silica gel in 5-40% ethyl acetate in hexanes to purify the desired product (80%, trace amount of o-alkylated product observed).

Workup

  1. additionaddition funnel
  2. stirringThe reaction was then stirred overnight at room temperature
  3. washwashed four times with water
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel in 5-40% ethyl acetate in hexanes
  8. customto purify the desired product (80%, trace amount of o-alkylated product observed)

Sources & evidence

ORD record
ord-f2da74112d484b2c99a2a6ba496b1a5f
Source dataset
uspto-grants-2010_08
Patent number
US07772235B2

Reaction notes

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