2-methylsulfanylacetyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred, cooled (-20°) solution of 10.2 g. (0.026 mol.) of 7-amino-3-[1-(2-carbamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid in 220 ml. of 3% sodium bicarbonate and 220 ml. of acetone is dropwise added a solution of 3.66 g. (0.029 mol.) of methylmercaptoacetyl chloride in 52 ml. of acetone, during which time the pH of the reaction mixture is maintained at 8.0 by addition of 10% sodium hydroxide. After addition the reaction mixture is stirred an additional 20 minutes at -15°, then is warmed to 25° and extracted with ether. The remaining aqueous phase is cooled, 250 ml. of ethyl acetate is added and the slurry is acidified with 3 N hydrochloric acid. The layers are separated and the aqueous phase is extracted twice more with ethyl acetate. The combined extracts are dried (MgSO4) and evaporated to dryness to yield the title compound. To a stirred, cooled (-20°) solution of 10.2 g After addition the reaction mixture is warmed to 25° extracted with ether The remaining aqueous phase is cooled of ethyl acetate is added The layers are separated the aqueous phase is extracted twice more with ethyl acetate The combined extracts are dried (MgSO4) evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred, cooled (-20°) solution of 10.2 g. (0.026 mol.) of 7-amino-3-[1-(2-carbamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid in 220 ml. of 3% sodium bicarbonate and 220 ml. of acetone is dropwise added a solution of 3.66 g. (0.029 mol.) of methylmercaptoacetyl chloride in 52 ml. of acetone, during which time the pH of the reaction mixture is maintained at 8.0 by addition of 10% sodium hydroxide. After addition the reaction mixture is stirred an additional 20 minutes at -15°, then is warmed to 25° and extracted with ether. The remaining aqueous phase is cooled, 250 ml. of ethyl acetate is added and the slurry is acidified with 3 N hydrochloric acid. The layers are separated and the aqueous phase is extracted twice more with ethyl acetate. The combined extracts are dried (MgSO4) and evaporated to dryness to yield the title compound. To a stirred, cooled (-20°) solution of 10.2 g After addition the reaction mixture is warmed to 25° extracted with ether The remaining aqueous phase is cooled of ethyl acetate is added The layers are separated the aqueous phase is extracted twice more with ethyl acetate The combined extracts are dried (MgSO4) evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (Methylthio)acetyl chloride (5.6 g) was added portionwise to a solution of methyl 1-methyl-2-(phenylmethylene)hydrazine carboximidothioate hydroiodide (A) (10.4 g) in triethylamine (7.08 g) and dichloromethane (55 ml) and the mixture stirred at room temperature for 2 h. The mixture was washed with water and evaporated to give an oil which was chromatographed using 1:1 ether-petroleum ether (b.p. 60°-80°) followed by ether to give the title compound (4.6 g) as a cream solid, m.p. 68°-70°. The mixture was washed with water evaporated to give an oil which was chromatographed

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (Methylthio)acetyl chloride (5.6 g) was added portionwise to a solution of methyl 1-methyl-2-(phenylmethylene)hydrazine carboximidothioate hydroiodide (A) (10.4 g) in triethylamine (7.08 g) and dichloromethane (55 ml) and the mixture stirred at room temperature for 2 h. The mixture was washed with water and evaporated to give an oil which was chromatographed using 1:1 ether-petroleum ether (b.p. 60°-80°) followed by ether to give the title compound (4.6 g) as a cream solid, m.p. 68°-70°. The mixture was washed with water evaporated to give an oil which was chromatographed

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1.84 g quantity of 4-(2,3-dihydroxypropoxy)phenol was dissolved in 0.40 g of sodium hydroxide and 10 ml of 90% methanol. To the solution was added 1.11 g of 2-methylmercaptoacetyl chloride, and the mixture was refluxed for 6 hours. The reaction mixture was concentrated and the residue was extracted with chloroform. The chloroform layer was washed with water, dewatered with Glauber's salt and concentrated. The residue was recrystallized from benzene-petroleum ether, giving 2.25 g of 2-{4-(2,3-dihydroxypropoxy)phenoxy}ethyl methyl sulfide in 87.2% yield, M.P. 59° to 61° C. the mixture was refluxed for 6 hours The reaction mixture was concentrated the residue was extracted with chloroform The chloroform layer was washed with water concentrated The residue was recrystallized from benzene-petroleum ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1.84 g quantity of 4-(2,3-dihydroxypropoxy)phenol was dissolved in 0.40 g of sodium hydroxide and 10 ml of 90% methanol. To the solution was added 1.11 g of 2-methylmercaptoacetyl chloride, and the mixture was refluxed for 6 hours. The reaction mixture was concentrated and the residue was extracted with chloroform. The chloroform layer was washed with water, dewatered with Glauber's salt and concentrated. The residue was recrystallized from benzene-petroleum ether, giving 2.25 g of 2-{4-(2,3-dihydroxypropoxy)phenoxy}ethyl methyl sulfide in 87.2% yield, M.P. 59° to 61° C. the mixture was refluxed for 6 hours The reaction mixture was concentrated the residue was extracted with chloroform The chloroform layer was washed with water concentrated The residue was recrystallized from benzene-petroleum ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolved in 4 ml of dimethylformamide were 2.00 g of triethylamine and 2.11 g of 4-(3-ethoxy-2-hydroxypropoxy)aniline. To the solution was added 1.25 g of methylmercaptoacetyl chloride with ice-cooling and the mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated and the residue was extracted with chloroform. The chloroform layer was washed with water and concentrated. The resulting residue was purified by silica gel column chromatography using a 1:5 ethanol-chloroform mixture, giving 2.85 g of 4-(3-ethoxy-2-hydroxypropoxy)phenylcarbamoylmethyl methyl sulfide in 95.3% yield. cooling The reaction mixture was concentrated the residue was extracted with chloroform The chloroform layer was washed with water concentrated The resulting residue was purified by silica gel column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20.3 g (0.1 mole) of 6-(p-aminophenyl)-4,5-dihydro-5-methyl-3(2H)-pyridazinone were stirred with 14.9 g (0.12 mole) of 2-methylmercaptoacetyl chloride and 400 ml of absolute acetone for 10 hours at room temperature. The product was filtered off under suction at 10° C., washed with cold acetone and dried at 70° C. under reduced pressure. 12.5 g (43%) of 6-[p-(2-methylmercaptoacetylamino)phenyl]-4,5-dihydro-5-methyl-3(2H)-pyridazinone were obtained. Mp.: 220°-222° C. The product was filtered off under suction at 10° C. washed with cold acetone dried at 70° C. under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 20.3 g (0.1 mole) of 6-(p-aminophenyl)-4,5-dihydro-5-methyl-3(2H)-pyridazinone were stirred with 14.9 g (0.12 mole) of 2-methylmercaptoacetyl chloride and 400 ml of absolute acetone for 10 hours at room temperature. The product was filtered off under suction at 10° C., washed with cold acetone and dried at 70° C. under reduced pressure. 12.5 g (43%) of 6-[p-(2-methylmercaptoacetylamino)phenyl]-4,5-dihydro-5-methyl-3(2H)-pyridazinone were obtained. Mp.: 220°-222° C. The product was filtered off under suction at 10° C. washed with cold acetone dried at 70° C. under reduced pressure