Dimethyl Carbonate → Methyl 3-oxo-3-[4-(piperidin-1-yl)pyrimidin-2-yl]propanoate

HRID 655782Notes

Reaction equation

HRID 655782 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13](=[O:15])[CH3:14])[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:18][O:19][C:20](=O)[O:21]C>>[O:15]=[C:13]([C:9]1[N:8]=[C:7]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:12]=[CH:11][N:10]=1)[CH2:14][C:20]([O:19][CH3:18])=[O:21]

Participants

4

Reactant 3

HCID 12021Dimethyl CarbonateHCID 24758Sodium hydrideHCID 580749301-[4-(Piperidin-1-yl)pyrimidin-2-yl]ethanone2×

Product 1

HCID 58074905Methyl 3-oxo-3-[4-(piperidin-1-yl)pyrimidin-2-yl]propanoateYield 52%

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 1-[4-(piperidin-1-yl)pyrimidin-2-yl]ethanone (Intermediate 52, 0.6 g, 2.92 mmol) in dimethylcarbonate (10 mL), sodium hydride (0.281 g, 11.7 mmol, 60%) was added portion wise at 0-5° C. over a period of 10 min. The reaction mixture was heated to 90° C. for 4 h. The reaction mixture was quenched by adding ice water. The aqueous layer pH was adjusted to neutral with dilute HCl, the aqueous layer was extracted with ethyl acetate (2×50 mL). The organic layer was dried and concentrated. The crude product was purified by column chromatography (75% ethylacetate & pet ether) to obtain methyl 3-oxo-3-[4-(piperidin-1-yl)pyrimidin-2-yl]propanoate 0.4 g (52%).

Workup

  1. customThe reaction mixture was quenched
  2. additionby adding ice water
  3. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (75% ethylacetate & pet ether)

Sources & evidence

ORD record
ord-8e3d5437554c46c88e78c015a79fccaf
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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