Diethyl methylmalonate → Diethyl (3-oxo quinuclidin-2-yl)methyl-methylmalonate

HRID 2052294Notes

Reaction equation

HRID 2052294 reaction equation
[O-]CC.[Na+].[Na].[CH3:6][CH:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:18]=[C:19]1[C:24](=[O:25])[CH:23]2[CH2:26][CH2:27][N:20]1[CH2:21][CH2:22]2>C(O)C.C(O)(=O)C>[O:25]=[C:24]1[CH:23]2[CH2:26][CH2:27][N:20]([CH2:21][CH2:22]2)[CH:19]1[CH2:18][C:7]([CH3:6])([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

7

Reactant 4

HCID 11857Diethyl methylmalonateHCID 3229732-Methylene-3-quinuclidoneHCID 2723922Sodium ethoxideHCID 5360545Sodium

Product 1

HCID 54084773Diethyl (3-oxo quinuclidin-2-yl)methyl-methylmalonate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×

Procedure

Ethanolic sodium ethoxide, previously prepared from 2.9 g of metallic sodium and 100 ml of ethanol, was added to diethyl methyl-malonate, 50 g, and the mixture was refluxed for 30 min. then cooled to 5°. A solution of 2-methylenequinuclidin-3-one, 39.4 g, in ethanol, 50 ml, was then added dropwise and with stirring. After 16 hrs. at room temperature, the resulting solution was neutralized with acetic acid then subjected to evaporation at reduced pressure. Water, 100 ml was added and the mixture was extracted with chloroform. Evaporation of this solvent gave diethyl (3-oxo quinuclidin-2-yl)-methyl-methylmalonate, 72 g (81%), m.p., 58.4° (from petroleum ether). A solution of the foregoing compound, 72 g, in ethanol, 50 ml, was treated at 5° and with stirring with a solution of sodium borohydride, 3.55 g, in ethanol, 600 ml. The borohydride solution was added in small increments over a period of six hours. After 20 hours, the mixture was neutralized with concentrated hydrochloric acid, then subjected to evaporation at reduced pressure. The residue was taken up in 200 ml of water and extracted with chloroform. Evaporation of this solvent left a syrupy residue, 55 g, which consisted of the compound diethyl (3-hydroxyquinucldin-2-yl)methyl-methylmalonate; its methiodide salt, prepared with methyl iodide in acetone, has a m.p. of 228.2°.

Workup

  1. temperaturethe mixture was refluxed for 30 min.
  2. temperaturethen cooled to 5°
  3. customat room temperature
  4. customthen subjected to evaporation at reduced pressure
  5. additionWater, 100 ml was added
  6. extractionthe mixture was extracted with chloroform
  7. customEvaporation of this solvent

Sources & evidence

ORD record
ord-42c11bed95b4450fa31413167f1e4929
Source dataset
uspto-grants-1980_01
Patent number
US04183938

Reaction notes

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