Thiophene → 2-Amino-3-(2-chlorobenzoyl)-5-(2,3-dihydroxy-n-propyl)-thiophene

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Reaction Steps

45.7 g (0.4 mol) of 3,4-dihydro-2H-pyran-2-methanol are subjected to ozonolysis in 100 ml of anhydrous methylene chloride at -40° . Then 104.9 g (0.4 mol) of triphenylphosphine in 70 ml of anhydrous methylene chloride are added dropwise and the reaction mixture is slowly brought to ambient temperature over a period of 3 hours. After 12 hours the solvent is removed and the residue is thoroughly digested with ether and the triphenylphosphine oxide precipitated is suction filtered. Any unreacted triphenylphosphine residues are precipitated in ether with methyl iodide in the form of the phosphonium salt and then suction filtered. The solvent is removed from the filtrate and the residue is fractionated in vacuo. 32 g (55% yield) of the 4-formyloxy-5-hydroxypentanal are obtained, bp0.1 =82°-92° C. 23 g (0.157 mol) of the aldehyde, 28 g (0.137 mol) of 0-chlorocyanoacetophenone, 5 g (0.157 mol) of sulphur and 16 g (0.157 mol) of triethylamine are used for the thiophene cyclisation in 100 ml of DMF in the usual way and the resulting 2-amino-3-(2-chlorobenzoyl)-5-(2-formyloxy-3-hydroxy-n-propyl)thiophene is refluxed for 2 hours, as the crude product, with 15 g (0.16 mol) of potassium hydroxide in 500 ml of methanol. After removal of the solvent, the residue is taken up in ethyl acetate, washed with water and dried and after the removal of the solvent chromatographed on silica gel with ethyl acetate as eluant. 19.9 g (total yield 39%) of 2-amino-3-(2-chlorobenzoyl)-5-(2,3-dihydroxy-n-propyl)-thiophene are obtained, m.p. 136°-137° C.

Provenance & Evidence