Methyl iodide → tert-butyl 1-acetyl-7-methyl-3-(methylsulfanyl)-4-oxo-6,7-dihydrothieno[3,4-c]pyridine-5(4H)-carboxylate

HRID 589997Notes

Reaction equation

HRID 589997 reaction equation
[CH3:1][CH:2]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:5](=[O:15])[CH2:4][C:3]1=O.[C:17](=O)([O-])[O-].[Cs+].[Cs+].[C:23](=[S:25])=[S:24].Cl[CH2:27][C:28](=[O:30])[CH3:29].IC>CN(C=O)C>[C:28]([C:29]1[S:24][C:23]([S:25][CH3:17])=[C:4]2[C:3]=1[CH:2]([CH3:1])[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:5]2=[O:15])(=[O:30])[CH3:27]

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 6348Carbon DisulfideHCID 6571ChloroacetoneHCID 10796Cesium carbonateHCID 67516180Tert-butyl 5-methyl-2,4-dioxopiperidine-1-carboxylate

Product 1

HCID 69044175tert-butyl 1-acetyl-7-methyl-3-(methylsulfanyl)-4-oxo-6,7-dihydrothieno[3,4-c]pyridine-5(4H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

The tert-butyl 5-methyl-2,4-dioxopiperidine-1-carboxylate from Step 2 (3.65 g, 16.06 mmol) was dissolved in DMF (40.2 ml) and treated with cesium carbonate (15.70 g, 48.2 mmol). The mixture was evacuated under vacuum while stirring (10 min), then back-filled with nitrogen before being treated with the carbon disulfide (1.452 ml, 24.09 mmol) which caused an immediate color change from orange to red. This was stirred for 10 min, room temperature, before being cooled to 0° C. and treated with chloroacetone (1.279 ml, 16.06 mmol). This was stirred, 0° C., for 1 hr before being treated with iodomethane (1.105 ml, 17.67 mmol), allowed to warm to room temperature, and stirred for 18 hrs. The solvent was partially evaporated in vacuo, then the reaction mixture was diluted with CH2Cl2, washed with sat'd brine (×4), dried (Na2SO4), filtered and evaporated to give a dark red oil. This was chromatographed (SiO2, 0-30% EtOAc/hexanes) to give the title compound. 1H NMR (400 MHz, CDCl3) 4.22 (dd, J=13.2, 1.8 Hz, 1H), 3.76 (m, 1H), 3.60 (dd, J=13.2, 3.4 Hz, 1H), 2.63 (s, 3H), 2.50 (s, 3H), 1.57 (s, 9H), 1.30 (d, J=7.1 Hz, 3H).

Workup

  1. customThe mixture was evacuated under vacuum
  2. additionback-filled with nitrogen
  3. stirringThis was stirred for 10 min, room temperature
  4. stirringThis was stirred, 0° C., for 1 hr
  5. temperatureto warm to room temperature
  6. stirringstirred for 18 hrs
  7. customThe solvent was partially evaporated in vacuo
  8. additionthe reaction mixture was diluted with CH2Cl2
  9. washwashed with sat'd brine (×4)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated
  13. customto give a dark red oil
  14. customThis was chromatographed (SiO2, 0-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f7492048a91645d6a29cad404d8c25a9
Source dataset
uspto-grants-2016_01
Patent number
US09233977B2

Reaction notes

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