Methyl chloroformate → 4-Ethyl 1-methyl 3-oxopiperidine-1,4-dicarboxylate

HRID 1155340Notes

Reaction equation

HRID 1155340 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:10](=[O:19])[CH2:9]1)C1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:27]([O:29][CH3:30])=[O:28]>C(O)C.[Pd].O>[CH3:30][O:29][C:27]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:10](=[O:19])[CH2:9]1)=[O:28]

Participants

7

Reactant 3

HCID 6586Methyl chloroformateHCID 11430Potassium CarbonateHCID 419705Ethyl 3-oxo-1-(phenylmethyl)-4-piperidinecarboxylate

Product 1

HCID 105613714-Ethyl 1-methyl 3-oxopiperidine-1,4-dicarboxylateYield 92.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate (Iselin, B. M. and Hoffmann, K., Helv. Chim. Acta, 1954, 37, 178) (14.0 g; 47 mmol) in aqueous ethanol (300 ml; 50%) was hydrogenated (ca. 300 kPa) in a PARR hydrogenation apparatus by using a 10% Pd-C catalyst (1.4 g). The reaction mixture was filtered and evaporated to dryness in vacuo. To an ice cooled solution of the residue in water (50 ml) was added with stirring an iced solution of potassium carbonate (19.4 g; 140 mmol) in water (20 ml) followed by addition of methyl chloroformate (11.3 g; 120 mmol). Stirring was continued at 0° C. for 30 minutes and at 25° C. for 30 minutes. The mixture was extracted with three 100 ml portions of ether. The combined and dried (Na2SO4) ether phases were evaporated in vacuo to give 10.0 g of crude product. Ball-tube distillation at 40-130 Pa (oven temperature 170° C.) gave IVa (9.0 g; 84%) as a colourless oil, which slowly crystallized, m.p. 36°-38° C. IR (film): 2980-2850 (several bands, m-s), 1700 (s), 1655 (s), 1620 (m) cm-1. 1H NMR (CCl4): δ12.3 (1 H, s), 4.13 (q, J 7 Hz) and 4.0-3.9 (m) (a total of 4 H), 3,62 (3 H, s), 3,43 (2 H, t, J 6 Hz), 2.4-2.1 (2 H, m), 1.30 (3 H, t, J 7 Hz).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customevaporated to dryness in vacuo
  3. additionTo an ice cooled solution of the residue in water (50 ml) was added
  4. extractionThe mixture was extracted with three 100 ml portions of ether
  5. dry with materialdried (Na2SO4) ether phases
  6. customwere evaporated in vacuo

Sources & evidence

ORD record
ord-b9b754d100304f449f25977ce68d5d50
Source dataset
uspto-grants-1981_11
Patent number
US04301287

Reaction notes

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