2-sulfanylethyl acetate

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

Procedure: Using 2-chloro-2',4'-difluoroacetophenone (2.0 g, 0.010 mol), 2-acetoxyethanethiol (J. Chem. Soc., 1952, 817.) (1.5 g, 0.013 mol), potassium carbonate (1.8 g, 0.013 mol) and methanol (50 mol), 2-(2-acetoxyethyl)thio-2',4'-difluoroacetophenone (1.8 g, yield: 62.0%) was obtained as a colorless oil by similar procedures to Example 1.

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

Procedure: Using 2-chloro-2',4'-difluoroacetophenone (2.0 g, 0.010 mol), 2-acetoxyethanethiol (J. Chem. Soc., 1952, 817.) (1.5 g, 0.013 mol), potassium carbonate (1.8 g, 0.013 mol) and methanol (50 mol), 2-(2-acetoxyethyl)thio-2',4'-difluoroacetophenone (1.8 g, yield: 62.0%) was obtained as a colorless oil by similar procedures to Example 1.

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

Procedure: Hydrogen chloride gas was introduced into a mixture of 2-acetoxyethanethiol (24.0 g) and paraformaldehyde (6.0 g) at a moderate rate with external cooling for 3 hours. Calcium chloride (25 g) was added and the reaction mixture allowed to stand in a salt-ice bath for 4 hours. Methylene chloride (200 ml) was added, the reaction mixture filtered and the solvent evaporated with rigorous exclusion of moisture. The residual oil was distilled to give 2-acetyloxyethyl chloromethyl sulfide (18.5 g, bp 82°-87° C. at 3 mm Hg). with external cooling for 3 hours the reaction mixture filtered the solvent evaporated with rigorous exclusion of moisture The residual oil was distilled

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

Procedure: Hydrogen chloride gas was introduced into a mixture of 2-acetoxyethanethiol (24.0 g) and paraformaldehyde (6.0 g) at a moderate rate with external cooling for 3 hours. Calcium chloride (25 g) was added and the reaction mixture allowed to stand in a salt-ice bath for 4 hours. Methylene chloride (200 ml) was added, the reaction mixture filtered and the solvent evaporated with rigorous exclusion of moisture. The residual oil was distilled to give 2-acetyloxyethyl chloromethyl sulfide (18.5 g, bp 82°-87° C. at 3 mm Hg). with external cooling for 3 hours the reaction mixture filtered the solvent evaporated with rigorous exclusion of moisture The residual oil was distilled

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

Procedure: Into a 2 liter flask is placed 182 gm (1.5 mole) 2-mercaptoethyl acetate, 200 ml water, 300 ml heptane and 120 gm (0.5 mole) monomethyltin trichloride. To the above stirred mixture is added portionwise 126 gm (1.5 mole) sodium bicarbonate maintaining a pot temperature of 25°-40° C. by the addition rate. When addition is complete, allow to stir 1 hour at 25°-40° C. The layers are separated and the organic phase washed with 200 ml water. The heptane is removed under vacuum. A yield of 240 gm, monomethyltin tris(2-mercaptoethyl acetate) is obtained as a colorless oil. nD25 1.5575. Into a 2 liter flask is placed When addition The layers are separated the organic phase washed with 200 ml water The heptane is removed under vacuum

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

Procedure: Hydrogen chloride gas was introduced into a mixture of 2-acetoxyethanethiol (24.0 g) and paraformaldehyde (6.0 g) at a moderate rate with external cooling for 3 hours. Calcium chloride (25 g) was added and the reaction mixture allowed to stand in a salt-ice bath for 4 hours. Methylene chloride (200 ml) was added, the reaction mixture filtered and the solvent evaporated with rigorous exclusion of moisture. The residual oil was distilled to give 2-acetyloxyethyl chloromethyl sulfide (18.5 g, bp 82°-87° C. at 3 mm Hg). with external cooling for 3 hours the reaction mixture filtered the solvent evaporated with rigorous exclusion of moisture The residual oil was distilled

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

Procedure: Hydrogen chloride gas was introduced into a mixture of 2-acetoxyethanethiol (24.0 g) and paraformaldehyde (6.0 g) at a moderate rate with external cooling for 3 hours. Calcium chloride (25 g) was added and the reaction mixture allowed to stand in a salt-ice bath for 4 hours. Methylene chloride (200 ml) was added, the reaction mixture filtered and the solvent evaporated with rigorous exclusion of moisture. The residual oil was distilled to give 2-acetyloxyethyl chloromethyl sulfide (18.5 g, bp 82°-87° C. at 3 mm Hg). with external cooling for 3 hours the reaction mixture filtered the solvent evaporated with rigorous exclusion of moisture The residual oil was distilled

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

Procedure: Hydrogen chloride gas was introduced into a mixture of 2-acetoxyethanethiol (24.0 g) and paraformaldehyde (6.0 g) at a moderate rate with external cooling for 3 hours. Calcium chloride (25 g) was added and the reaction mixture allowed to stand in a salt-ice bath for 4 hours. Methylene chloride (200 ml) was added, the reaction mixture filtered and the solvent evaporated with rigorous exclusion of moisture. The residual oil was distilled to give 2-acetyloxyethyl chloromethyl sulfide (18.5 g, bp 82°-87° C. at 3 mm Hg). with external cooling for 3 hours the reaction mixture filtered the solvent evaporated with rigorous exclusion of moisture The residual oil was distilled

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

Procedure: The tert-butyl 4-(1-cyano-2-oxoethyl)piperidine-1-carboxylate (926 mg, 3.68 mmol) obtained in Step 4 of Example 1 was dissolved in dichloromethane (8 mL), a solution of triethylamine (0.66 mL, 4.78 mmol) and methanesulfonyl chloride (0.31 mL, 4.05 mmol) in dichloromethane (2 mL) was added dropwise under ice-cooling, followed by stirring under ice-cooling for 1 hour. The reaction liquid was diluted with chloroform, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The obtained residue (1.58 g) was dissolved in dichloromethane (20 mL), 1,8-diazabicyclo[4,3,0]-7-undecene (2.13 mL, 17.2 mmol) and 2-mercaptoethyl acetate (0.31 mL, 4.05 mmol) were added under ice-cooling, followed by stirring under ice-cooling for 3 hours. The reaction liquid was diluted with chloroform, and washed with a 1 N aqueous hydrochloric acid solution. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The obtained residue (3.26 g) was dissolved in ethanol (20 mL), and then sodium ethoxide (2.0 g, 29.4 mmol) was added, followed by heating under reflux for 3 hours. The reaction liquid was concentrated under a reduced pressure, and the obtained residue was dissolved in chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The obtained residue was purified by using silica gel chromatography (chloroform:methanol=50:1→30:1) to give tert-butyl 4-[4-amino-5-(ethoxycarbonyl)thiophen-3-yl]piperidine-1-carboxylate (287 mg, 22.0%) as a pale yellow amorphous. cooling cooling for 1 hour The reaction liquid the organic layer was washed with saturated brine dried over anhydrous sodium sulfate concentrated under a reduced pressure The obtained residue (1.58 g) was dissolved in dichloromethane (20 mL) cooling by stirring under ice- cooling for 3 hours The reaction liquid washed with a 1 N aqueous hydrochloric acid solution The organic layer was washed with saturated brine dried over anhydrous sodium sulfate concentrated under a reduced pressure The obtained residue (3.26 g) was dissolved in ethanol (20 mL) by heating under reflux for 3 hours The reaction liquid was concentrated under a reduced pressure the obtained residue was dissolved in chloroform The organic layer was washed with saturated brine dried over anhydrous sodium sulfate concentrated under a reduced pressure The obtained residue was purified

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

Procedure: Using 2-chloro-2',4'-difluoroacetophenone (2.0 g, 0.010 mol), 2-acetoxyethanethiol (J. Chem. Soc., 1952, 817.) (1.5 g, 0.013 mol), potassium carbonate (1.8 g, 0.013 mol) and methanol (50 mol), 2-(2-acetoxyethyl)thio-2',4'-difluoroacetophenone (1.8 g, yield: 62.0%) was obtained as a colorless oil by similar procedures to Example 1.

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

Procedure: Into a 2 liter flask placed 182 gm (1.5 mole) 2-mercaptoethyl acetate, 200 ml water, 300 ml heptane and 120 gm (0.5 mole) monomethyltin trichloride. To the above stirred mixture is added portionwise 126 gm (1.5 mole) sodium bicarbonate maintaining a pot temperature of 25°-40° C. by the addition rate. When addition is complete, allow to stir 1 hour at 25°-40° C. The layers are separated and the organic plase washed with 200 ml water. The heptane is removed under vacuum. A yield of 240 gm, monomethyltin tris(2-mercaptoethylacetate) is obtained as a colorless oil. nD25 1.5575. Into a 2 liter flask placed When addition The layers are separated the organic plase washed with 200 ml water The heptane is removed under vacuum

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

Procedure: Using 2-chloro-2',4'-difluoroacetophenone (2.0 g, 0.010 mol), 2-acetoxyethanethiol (J. Chem. Soc., 1952, 817.) (1.5 g, 0.013 mol), potassium carbonate (1.8 g, 0.013 mol) and methanol (50 mol), 2-(2-acetoxyethyl)thio-2',4'-difluoroacetophenone (1.8 g, yield: 62.0%) was obtained as a colorless oil by similar procedures to Example 1.