Ammonium Chloride → Diethyl 5-ethylpyridine-2,3-dicarboxylate

HRID 1449459Notes

Reaction equation

HRID 1449459 reaction equation
C(O[CH:4]=[C:5]([C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=O)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.O1CC[N:21]([CH:24]=[CH:25][CH2:26][CH3:27])CC1.[NH4+].[Cl-]>CO.C(O)(=O)C>[CH2:26]([C:25]1[CH:4]=[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:21][CH:24]=1)[CH3:27]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 40590Diethyl 2-(ethoxymethylidene)-3-oxobutanedioateHCID 5809771-Morpholinobutene

Product 1

HCID 10857926Diethyl 5-ethylpyridine-2,3-dicarboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

To a solution of diethyl ethoxymethyleneoxalacetate (43.2 g, 0.16 mol) dissolved in CH3OH (150 mL) at -10° under N2 is added 1-morpholinobutene (25 g, 0.16 mol). The reaction is slowly warmed to room temperature over three hours, after which the CH3OH is removed in vacuo. The residue is dissolved in acetic acid (100 mL) and this solution slowly added to NH4Cl (34.2 g, 0.64 mol) dissolved in acetic acid (200 mL) at 50°-70°. The reaction is then heated to 90°-95° for two hours and 30 minutes, concentrated in vacuo, partitioned between water and the CH2Cl2, add the organic phase chromatographed over silica gel with CH2Cl2 --CH3CN (95:5) elution to give the product as an oil. Distillation at 123°-155° at 0.15 mm gives the product (23.4 g, 83% pure, 55%).

Workup

  1. customafter which the CH3OH is removed in vacuo
  2. dissolutionThe residue is dissolved in acetic acid (100 mL)
  3. temperatureThe reaction is then heated to 90°-95° for two hours and 30 minutes
  4. concentrationconcentrated in vacuo
  5. custompartitioned between water
  6. additionthe CH2Cl2, add the organic phase
  7. customchromatographed over silica gel with CH2Cl2 --CH3CN (95:5) elution

Sources & evidence

ORD record
ord-fe9cf4876665485499bf8c7f1bdc0d12
Source dataset
uspto-grants-1997_02
Patent number
US05599772

Reaction notes

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