Dimethylformamide → Ethyl 5-formylthiophene-2-carboxylate

HRID 660969

Reaction equation

HRID 660969 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:15][C:16]([C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)=[O:17])[CH3:14].CN(C)[CH:25]=[O:26]>C1COCC1>[CH2:13]([O:15][C:16]([C:18]1[S:19][C:20]([CH:25]=[O:26])=[CH:21][CH:22]=1)=[O:17])[CH3:14]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 76052Ethyl 2-thenoateHCID 178418339Butyllithium

Product 1

HCID 10797570Ethyl 5-formylthiophene-2-carboxylateYield 55.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of diisopropylamine (0.588 mL, 60 mmol) in THF (20 mL) under N2 is cooled to −78° C. and treated with n-butyllithium (2.5 M in hexanes, 1.66 mL). The mixture is then warmed to 0° C. for 10 min, cooled back to −78° C., treated dropwise with a solution of thiophene-2-carboxylic acid ethyl ester (0.5 g, 3.2 mmol) in THF (12 mL), and stirred 5 min. N,N-dimethylformamide (0.324 mL, 4.16 mmol) is then added, and the reaction is allowed to warm to rt, while stirring overnight. Aqueous buffer (pH=7) is added, and the product is extracted into ethyl acetate (3×). Combined organic layers are dried, filtered, and concentrated. The resulting residue is applied to silica gel and eluted using hexanes with an ethyl acetate gradient from 0% to 40% to give 5-formyl-thiophene-2-carboxylic acid ethyl ester (325 mg).

Workup

  1. temperaturecooled back to −78° C.
  2. temperatureto warm to rt
  3. stirringwhile stirring overnight
  4. additionAqueous buffer (pH=7) is added
  5. extractionthe product is extracted into ethyl acetate (3×)
  6. customCombined organic layers are dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washeluted

Sources & evidence

ORD record
ord-162645bf6d3144bb95b74988208de3dd
Source dataset
uspto-grants-2011_12
Patent number
US08084489B2

Linked notes

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