2-Acetylthiophene → Ethyl 3-oxo-3-(thiophen-2-yl)propanoate

HRID 1620019Notes

Reaction equation

HRID 1620019 reaction equation
[H-].[Na+].[C:3](=[O:10])([O:7][CH2:8][CH3:9])OCC.[C:11]([C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)(=[O:13])[CH3:12].[H][H]>C1C=CC=CC=1>[O:13]=[C:11]([C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)[CH2:12][C:3]([O:7][CH2:8][CH3:9])=[O:10]

Participants

6

Reactant 4

HCID 69202-AcetylthiopheneHCID 7766Diethyl CarbonateHCID 24758Sodium hydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 255159Ethyl 3-oxo-3-(thiophen-2-yl)propanoateYield 69.2%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

To a suspension of sodium hydride (7.13 g, 178 mmol, 60% in mineral oil) in benzene (100 mL) was added diethyl carbonate (14.0 g, 118 mmol). The mixture was heated to reflux and a solution of 2-acetylthiophene (7.48 g, 59.4 mmol) in benzene (20 mL) was added dropwise over 1 hour. When addition was complete, the mixture was refluxed for a further 3 hours, after which hydrogen evolution had ceased. The reaction was quenched with acetic acid (15 mL) and then with ice-cold water (45 mL). The organic phase was separated, the aqueous layer was extracted with benzene and the combined extracts were washed with cold water, dried (Na2SO4) and concentrated under reduced pressure. The residue was distilled under high vacuum to give 36 (8.15 g, 69%) as a colorless oil: by 130° C. (0.3 torr): IR (neat) 2925, 2848, 1742, 1669, 1459, 1373, 1030, 851, 723 cm−1; 1H NMR (400 MHz, CHCl3) δ 1.28 (t, 3H, J=7 Hz), 3.93 (s, 2H), 4.25 (q, J=Hz, 2H), 7.16 (m, 1H), 7.71-7.76 (m, 2H); 13C NMR (300 MHz, CDCl3) δ 14.1, 46.5, 61.6, 128.3, 133.2, 134.9, 142.4, 167.0, 185.2: HRMS (EI) m/z 198.0349 (calcd for C9H10O3S 198.0351).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. additionWhen addition
  4. temperaturethe mixture was refluxed for a further 3 hours
  5. customThe reaction was quenched with acetic acid (15 mL)
  6. customThe organic phase was separated
  7. extractionthe aqueous layer was extracted with benzene
  8. washthe combined extracts were washed with cold water
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated under reduced pressure
  11. distillationThe residue was distilled under high vacuum

Sources & evidence

ORD record
ord-010e9d4b94b048af867ca066961b73a3
Source dataset
uspto-grants-2014_07
Patent number
US08772330B2

Reaction notes

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