ethyl 2-methoxyethanimidate;hydrochloride

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

Procedure: [step 1] 3,4-Diaminothiophene dihydrochloride (300 mg, 1.60 mmol) was suspended in ethanol (12 mL), triethylamine (0.45 mL, 3.21 mmol) and ethyl 2-methoxyacetimidate monohydrochloride (Journal of Medicinal Chemistry, 1991, vol. 34, p 2468; 906 mg, 4.01 mmol) were added, and the mixture was stirred at room temperature for 70 hr. To the mixture was added saturated aqueous sodium hydrogen carbonate, and the mixture was extracted 3 times with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 v/v-0/100 v/v) to give 2-(methoxymethyl)-1H-thieno[3,4-d]imidazole (156 mg, 58%). 906 mg, 4.01 mmol) were added the mixture was extracted 3 times with chloroform The combined organic layers were dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0 v/v-0/100 v/v)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 2-methoxyacetimidate hydrochloride (0.95 g, 6.18 mmol) was suspended in DCM (12.4 mL) and the mixture was cooled to 0° C. Pyridine (2.5 mL, 30.9 mmol) and ethyl chloroformate (1.2 mL, 12.4 mmol) were added sequentially and the solution was allowed to warm to RT and stirred for 12 h. EtOAc (100 mL) was added and solids were removed by filtration through a pad of diatomaceous earth. The filtrate was concentrated in vacuo to afford ethyl N-ethoxycarbonyl-2-methoxyacetimidate (1.2 g, 100%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 4.08-4.03 (m, 2H), 3.90 (q, J=7.0 Hz, 4H), 3.20 (s, 3H), 1.11 (t, J=6.9 Hz, 6H). to warm to RT solids were removed by filtration through a pad of diatomaceous earth The filtrate was concentrated in vacuo

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

Procedure: 2-Methoxyacetonitrile (1.0 g, 14.1 mmol) was dissolved in anhydrous ethanol (28.1 mL) under an atmosphere of Ar. The solution was cooled to 0° C., saturated with HCl gas, stirred for 6 h, allowed to warm to RT, and stirred for 6 h. The solvent was removed in vacuo to afford ethyl 2-methoxyacetimidate hydrochloride (1.0 g, 44.0%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 4.42 (q, J=7.0 Hz, 2H), 4.31 (s, 2H), 3.36 (s, 3H), 1.32 (t, J=7.0 Hz, 3H). stirred for 6 h The solvent was removed in vacuo

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

Procedure: 2-Methoxyacetonitrile (1.0 g, 14.1 mmol) was dissolved in anhydrous ethanol (28.1 mL) under an atmosphere of Ar. The solution was cooled to 0° C., saturated with HCl gas, stirred for 6 h, allowed to warm to RT, and stirred for 6 h. The solvent was removed in vacuo to afford ethyl 2-methoxyacetimidate hydrochloride (1.0 g, 44.0%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 4.42 (q, J=7.0 Hz, 2H), 4.31 (s, 2H), 3.36 (s, 3H), 1.32 (t, J=7.0 Hz, 3H). stirred for 6 h The solvent was removed in vacuo

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrochloric acid gas is bubbled through a solution of methoxyacetonitrile (26 g, 0.37 mol) in EtOH (22 mL) and diethyl ether (118 mL), which is chilled to −10° C. for twenty minutes. The reaction vessel is capped and stirred for 17 hours at ambient temperature. The mixture is cooled to −10° C. The solid that forms is collected by filtration, washed with diethyl ether and air dried to afford 2-methoxy-acetimidic acid ethyl ester hydrochloride (49.3 g, 87%) as a solid. The reaction vessel is capped The mixture is cooled to −10° C The solid that forms is collected by filtration washed with diethyl ether and air dried

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrochloric acid gas is bubbled through a solution of methoxyacetonitrile (26 g, 0.37 mol) in EtOH (22 mL) and diethyl ether (118 mL), which is chilled to −10° C. for twenty minutes. The reaction vessel is capped and stirred for 17 hours at ambient temperature. The mixture is cooled to −10° C. The solid that forms is collected by filtration, washed with diethyl ether and air dried to afford 2-methoxy-acetimidic acid ethyl ester hydrochloride (49.3 g, 87%) as a solid. The reaction vessel is capped The mixture is cooled to −10° C The solid that forms is collected by filtration washed with diethyl ether and air dried

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

Procedure: A 307.2 gm. portion of ethyl 2-methoxyacetimidate hydrochloride [Rule, J. Chem. Soc. 113, 9 (1918)] and 180 gm. of 1,3-dihydroxyacetone in 1 liter of liquid ammonia are reacted as described in Example 3 giving the desired product as an oil. A crystalline picrate salt (m.p. 175°-178° C.) is obtained by heating the oily product and picric acid in water.

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

Procedure: A 307.2 gm. portion of ethyl 2-methoxyacetimidate hydrochloride [Rule, J. Chem. Soc. 113, 9 (1918)] and 180 gm. of 1,3-dihydroxyacetone in 1 liter of liquid ammonia are reacted as described in Example 3 giving the desired product as an oil. A crystalline picrate salt (m.p. 175°-178° C.) is obtained by heating the oily product and picric acid in water.

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydrochloric acid gas is bubbled through a solution of methoxyacetonitrile (26 g, 0.37 mol) in EtOH (22 mL) and diethyl ether (118 mL), which is chilled to −10° C. for twenty minutes. The reaction vessel is capped and stirred for 17 hours at ambient temperature. The mixture is cooled to −10° C. The solid that forms is collected by filtration, washed with diethyl ether and air dried to afford 2-methoxy-acetimidic acid ethyl ester hydrochloride (49.3 g, 87%) as a solid. The reaction vessel is capped The mixture is cooled to −10° C The solid that forms is collected by filtration washed with diethyl ether and air dried

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

Procedure: A 307.2 gm. portion of ethyl 2-methoxyacetimidate hydrochloride [Rule, J. Chem. Soc. 113, 9 (1918)] and 180 gm. of 1,3-dihydroxyacetone in one liter of liquid ammonia are reacted as described in Example 3 giving the desired product as an oil. A crystalline picrate salt (m.p. 175°-178° C.) is obtained by heating the oily product and picric acid in water.

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

Procedure: A 307.2 gm. portion of ethyl 2-methoxyacetimidate hydrochloride [Rule, J. Chem. Soc. 113, 9 (1918)] and 180 gm. of 1,3-dihydroxyacetone in one liter of liquid ammonia are reacted as described in Example 3 giving the desired product as an oil. A crystalline picrate salt (m.p. 175°-178° C.) is obtained by heating the oily product and picric acid in water.

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

Procedure: A 307.2 gm. portion of ethyl 2-methoxyacetimidate hydrochloride [Rule, J. Chem. Soc. 113, 9 (1918)] and 180 gm. of 1,3-dihydroxyacetone in 1 liter of liquid ammonia are reacted as described in Example 3 giving the desired product as an oil. A crystalline picrate salt (m.p. 175°-178° C.) is obtained by heating the oily product and picric acid in water.