L-Methionine → tert-Butyl 1-acetyl-3-(methylsulfanyl)-4-oxo-6,7-dihydrothieno[3,4-c]pyridine-5(4H)-carboxylate

HRID 589988Notes

Reaction equation

HRID 589988 reaction equation
[C:1]([O-])([O-])=O.[Cs+].[Cs+].[O:7]=[C:8]1[CH2:13][C:12](=O)[CH2:11][CH2:10][N:9]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].[C:22](=[S:24])=[S:23].Cl[CH2:26][C:27](=[O:29])[CH3:28].N[C@H](C(O)=O)CCSC>CN(C=O)C>[C:27]([C:28]1[S:23][C:22]([S:24][CH3:1])=[C:13]2[C:12]=1[CH2:11][CH2:10][N:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:8]2=[O:7])(=[O:29])[CH3:26]

Participants

7

Reactant 5

HCID 6137L-MethionineHCID 6348Carbon DisulfideHCID 6571ChloroacetoneHCID 10796Cesium carbonateHCID 23730999tert-Butyl 2,4-dioxopiperidine-1-carboxylate

Product 1

HCID 86701088tert-Butyl 1-acetyl-3-(methylsulfanyl)-4-oxo-6,7-dihydrothieno[3,4-c]pyridine-5(4H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of Cs2CO3 (2.29 g, 7.03 mmol) in DMF (6 mL) at rt was added tert-butyl 2,4-dioxopiperidine-1-carboxylate (0.50 g, 2.35 mmol). The mixture was stirred at rt for 10 min. Carbon disulfide (0.21 mL, 3.5 mmol) was then added and the reaction mixture was stirred at rt for an additional 10 min. After cooling in an ice bath, a solution of chloroacetone (0.19 mL, 2.35 mmol) in DMF (6 mL) was added. After 1 h, a solution of Met (0.16 mL, 2.58 mmol) in DMF (3 mL) was added and the reaction mixture was warmed to rt and stirred overnight. The mixture was quenched with water (25 mL) and vigorously stirred for 10 h. The resulting mixture was concentrated in vacuo to remove DMF, partitioned between CH2Cl2 and water and filtered. The filtrate was washed with water, dried (Na2SO4) and concentrated. Purification by silica gel chromatography (gradient elution, 0-30% EtOAc/hexanes) afforded the title compound. LRMS (ESI) m/z 342.0 [(M+H)+; calcd for C15H19NO4S2: 342],

Workup

  1. stirringthe reaction mixture was stirred at rt for an additional 10 min
  2. temperatureAfter cooling in an ice bath
  3. waitAfter 1 h
  4. temperaturethe reaction mixture was warmed to rt
  5. stirringstirred overnight
  6. customThe mixture was quenched with water (25 mL)
  7. stirringvigorously stirred for 10 h
  8. concentrationThe resulting mixture was concentrated in vacuo
  9. customto remove DMF
  10. custompartitioned between CH2Cl2 and water
  11. filtrationfiltered
  12. washThe filtrate was washed with water
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated
  15. customPurification
  16. washby silica gel chromatography (gradient elution, 0-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-631b4f5dd9f84302b05d59d8e94d502d
Source dataset
uspto-grants-2016_01
Patent number
US09233977B2

Reaction notes

Loading…