Acetic Acid → HCID 16744634, compound

Participants

Reaction Conditions

Reaction Steps

At 0-10° C., 61.3 g of methyl 3-mercaptopropionate (3, 0.5 mol, content: 98%) were added dropwise over 35 min to 90 g of a 30% solution of NaOMe in methanol (0.5 mol). After the addition, the mixture was stirred at 0-10° C. for a further 10 min and subsequently, at 0-5° C., 63.2 g of methyl 2-chloropropionate (4, 0.5 mol, content: 97%) were metered in over 50 min. The reaction mixture was stirred at 0-5° C. for a further 30 min, before 500 ml of xylene were added. Subsequently, the methanol was substantially distilled off. 99 g of a 30% solution of NaOMe in methanol (0.55 mol) were added dropwise at approx. 90° C. over 75 min to the resulting suspension, and methanol continued to be distilled off at the same time. The reaction mixture was then cooled to 80° C. under argon before 33 g of acetic acid (0.55 mol) were metered in. On completion of addition, 500 ml of water were added at 70° C. and the mixture was subsequently cooled to room temperature. After the separation of the phases, the aqueous phase was reextracted once more with 250 ml of xylene and the combined organic phases were subsequently washed once more with 100 ml of water. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. The residue was admixed with 830 ml of methanol and 94.6 g of ammonium formate (1.5 mol) and then heated to reflux. After 12 h under reflux, the workup was effected by substantial concentration. The residue was taken up in 500 ml of water and extracted three times with 200 ml each time of dichloromethane. The combined organic phases were dried (Na2SO4). After the solvent had been distilled off under reduced pressure, 81 g of methyl 4-amino-5-methyl-2,5-dihydrothiophene-3-carboxylate (2) were obtained (68% of theory over all stages, content: 72.5%).

Provenance & Evidence