Water → 5-Ethyl-2-thiophenecarboxylic acid, N-t-butyl amide

HRID 235083

Reaction equation

HRID 235083 reaction equation
[CH2:1]([C:3]1[S:7][C:6]([C:8]([OH:10])=O)=[CH:5][CH:4]=1)[CH3:2].S(Cl)(Cl)=O.[C:15]([NH2:19])([CH3:18])([CH3:17])[CH3:16].O>C(Cl)Cl.CCCCCC>[C:15]([NH:19][C:8]([C:6]1[S:7][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=1)=[O:10])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 962WaterHCID 6385Tert-ButylamineHCID 24386Thionyl ChlorideHCID 5881925-Ethylthiophene-2-carboxylic acid

Product 1

HCID 606993245-Ethyl-2-thiophenecarboxylic acid, N-t-butyl amideYield 80%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 28 g (0.18 mol) of 5-ethyl-2-thiophenecarboxylic acid, from step 3a above, in 130 mL of methylene chloride was added a large excess (130 mL, 10 mol) of thionyl chloride, and the solution was heated at reflux for 2 hours. The solvent and excess reagent were removed by evaporation, and the residue was dissolved in 130 mL of chloroform and cooled to 0° C. To this solution was added 94 mL (0.9 mol) of t-butylamine dropwise, and the solution was stirred at reflux for 2 hours. The reaction was cooled, the solution poured into water, and the mixture extracted with ethyl acetate. The extract was washed with water and brine, dried, and concentrated. The residue was dissolved in ethyl acetate and the crude product was precipitated by addition of hexane. The crude product was collected by filtration and purified by flash chromatography over silica gel, eluting with 1:6 ethyl acetate:hexane, to afford 13.3 g (80% yield) of the title product after drying. MS 212 (M+H)+. NMR (CDCl3) δ: 7.25 (d, 1H, J=3 Hz), 6,72 (d, 1H, J=3 Hz), 5.70 (bs, 1H), 2.84 (q, 2H, J=7 Hz), 1.45 (s, 9H), 1.31 (t, 3H, J=7 Hz).

Workup

  1. temperaturethe solution was heated
  2. temperatureat reflux for 2 hours
  3. customThe solvent and excess reagent were removed by evaporation
  4. dissolutionthe residue was dissolved in 130 mL of chloroform
  5. temperatureat reflux for 2 hours
  6. temperatureThe reaction was cooled
  7. extractionthe mixture extracted with ethyl acetate
  8. washThe extract was washed with water and brine
  9. customdried
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved in ethyl acetate
  12. customthe crude product was precipitated by addition of hexane
  13. filtrationThe crude product was collected by filtration
  14. custompurified by flash chromatography over silica gel
  15. washeluting with 1:6 ethyl acetate

Sources & evidence

ORD record
ord-23b6fc38c21d44bf962b28e9020bf8fb
Source dataset
uspto-grants-1997_01
Patent number
US05597832

Linked notes

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