Dimethyl Carbonate → HCID 66653516, compound

HRID 242323Notes

Reaction equation

HRID 242323 reaction equation
[H-].[Na+].[C:3](=[O:8])([O:6][CH3:7])OC.[CH3:9][O:10][C:11]1[N:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]2)=[CH:13][C:12]=1[CH3:24]>>[CH3:7][O:6][C:3]([CH:19]1[C:20](=[O:23])[CH2:21][CH2:22][N:17]([C:14]2[CH:15]=[N:16][C:11]([O:10][CH3:9])=[C:12]([CH3:24])[CH:13]=2)[CH2:18]1)=[O:8]

Participants

4

Reactant 3

HCID 12021Dimethyl CarbonateHCID 24758Sodium hydrideHCID 66653450HCID 66653450, compound

Product 1

HCID 66653516HCID 66653516, compoundYield 77.2%

Conditions

Temperature
90 °C

Procedure

To a stirred suspension of sodium hydride (60%, 153 mg, 6.36 mmol) in dimethyl carbonate (3.82 mL, 45.4 mmol) at room temperature was slowly added 6′-methoxy-5′-methyl-2,3,5,6-tetrahydro-[1,3′]bipyridinyl-4-one (1 g, 4.54 mmol). The reaction mixture was heated to reflux (90° C.) for 1 h and then cooled to room temperature. The mixture was partitioned between CH2Cl2 and water and a solution of 1N HCl was added cautiously. The aqueous layer was separated and washed with an addition portion of CH2Cl2. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and evaporated to give the crude product, which was purified by flash-chromatography on silica gel (heptane/ethylacetate 3/1) to afford 6′-methoxy-5′-methyl-4-oxo-3,4,5,6-tetrahydro-2H-[1,3′]bipyridinyl-3-carboxylic acid methyl ester (975 mg, yield 77%) as a white solid. 1H-NMR (400 MHz, DMSO, 298K) (mixture of keto and enol tautomers observed) δ ppm 2.12 (s, 6H) 2.36-2.69 (m, 4H) 3.26-3.96 (m, 20H) 7.34-7.77 (m, 4H) 11.84 (s, 1H). LCMS: [M+H]+=279.1, Rt(3)=1.51 min (tautomer 1) and 1.70 min (tautomer 2).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperaturecooled to room temperature
  3. customThe mixture was partitioned between CH2Cl2 and water
  4. additiona solution of 1N HCl was added cautiously
  5. customThe aqueous layer was separated
  6. washwashed with an addition portion of CH2Cl2
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customto give the crude product, which
  12. customwas purified by flash-chromatography on silica gel (heptane/ethylacetate 3/1)

Sources & evidence

ORD record
ord-5f3027baa86d41f493b1b13230ffa80e
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

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