Tetrahydrofuran → HCID 68183095, compound

HRID 1615504Notes

Reaction equation

HRID 1615504 reaction equation
[H-].[Na+].O1CCCC1.[C:8](=[O:13])([O:11][CH3:12])OC.[N:14]1[CH:19]=[CH:18][C:17]([C:20]2[S:24][C:23]([C:25](=[O:27])[CH3:26])=[CH:22][CH:21]=2)=[CH:16][CH:15]=1>>[O:27]=[C:25]([C:23]1[S:24][C:20]([C:17]2[CH:18]=[CH:19][N:14]=[CH:15][CH:16]=2)=[CH:21][CH:22]=1)[CH2:26][C:8]([O:11][CH3:12])=[O:13]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 12021Dimethyl CarbonateHCID 24758Sodium hydrideHCID 46317398HCID 46317398, compound

Product 1

HCID 68183095HCID 68183095, compoundYield 38.3%

Conditions

Temperature
60 °C

Procedure

To a 100 mL round bottom flask was added a suspension of sodium hydride (0.1574 g, 3.936 mmol) in tetrahydrofuran (16.000 mL, 197.26 mmol). Dimethyl carbonate (0.663 mL, 7.872 mmol) was added followed by 1-(5-pyridin-4-yl-2-thienyl)ethanone (0.400 g, 1.968 mmol) which was added in portions. The red reaction mixture was heated to 60° C. and allowed to stir for 18 hours. The reaction was cooled to ambient temperature and quenched by the dropwise addition of water (5.00 mL). The mixture was neutralized to pH 7 by the addition of a saturated aqueous solution of ammonium chloride (10.00 mL) and extracted with EtOAc (70.00 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was dry loaded onto silica gel and then purified using ISCO (12 g cartridge, gradient hexanes to 100% EtOH over 30 min) to afford the title compound (0.197 g, 36%) as a yellow oil. LC/MS (AA) ES+ 262. 1H NMR (dmso-d6, 400 MHz): δ 8.67-8.65 (m, 2H), 8.08 (d, 1H), 7.94 (d, 1H), 7.78-7.77 (m, 2H), 4.20 (s, 2H), 3.67 (s, 3H).

Workup

  1. additionTo a 100 mL round bottom flask was added
  2. additionwas added in portions
  3. customThe red reaction mixture
  4. temperatureThe reaction was cooled to ambient temperature
  5. customquenched by the dropwise addition of water (5.00 mL)
  6. additionThe mixture was neutralized to pH 7 by the addition of a saturated aqueous solution of ammonium chloride (10.00 mL)
  7. extractionextracted with EtOAc (70.00 mL×3)
  8. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. dry with materialThe crude material was dry
  12. custompurified
  13. customISCO (12 g cartridge, gradient hexanes to 100% EtOH over 30 min)

Sources & evidence

ORD record
ord-761d6411aea44e19a9ccc9a8acfa168e
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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