ethyl 2-methylpropanimidate;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The method according to claim 1 wherein ethyl isobutyrimidate hydrochloride is neutralized by trimethylamine dissolved in toluene, the free ethyl isobutyrimidate is freed from water by azeotropic distillation; then the dry ethyl isobutyrimidate in toluene is reacted with an excess of diketene dissolved in toluene in the presence of trimethylamine and the resulting organic solution is treated with gaseous ammonia, in molar equivalent amounts and subsequent azeotropic removal of water to form 2-isopropyl-4-methyl-6-hydroxypyrimidine which is dried and recovered from said organic solvent. the free ethyl isobutyrimidate is freed from water by azeotropic distillation then the dry ethyl isobutyrimidate in toluene is reacted with an excess of diketene

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The method according to claim 1 wherein ethyl isobutyrimidate hydrochloride is neutralized by trimethylamine dissolved in toluene, the free ethyl isobutyrimidate is freed from water by azeotropic distillation; then the dry ethyl isobutyrimidate in toluene is reacted with an excess of diketene dissolved in toluene in the presence of trimethylamine and the resulting organic solution is treated with gaseous ammonia, in molar equivalent amounts and subsequent azeotropic removal of water to form 2-isopropyl-4-methyl-6-hydroxypyrimidine which is dried and recovered from said organic solvent. the free ethyl isobutyrimidate is freed from water by azeotropic distillation then the dry ethyl isobutyrimidate in toluene is reacted with an excess of diketene

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 1-imino-1-ethoxyisobutane hydrochloride (610.0 g) in ether (12.5 L) was added ethanol (1940.0 g, 10 mol). The mixture was stirred at 35°-37° C. under N2 for 72 hours. The reaction mixture was filtered, the filtrate was washed with a 10% sodium carbonate solution, followed by a saturated sodium carbonate solution and the organic layer was dried over K2CO3. The organic layer was concentrated in vacuo and the residue was dissolved in ether, filtered and the filtrate was washed successively with a 10% NaOH solution and water. The organic layer was dried over K2CO3, the solvent was removed in vacuo and the residue was diluted with hexane, cooled in an ice-bath and filtered. The filtrate was concentrated in vacuo and the residue was distilled at 70°-72° C. (27 mmHg) to afford 320 g (42%) of 1,1,1-triethoxyisobutane. The reaction mixture was filtered the filtrate was washed with a 10% sodium carbonate solution the organic layer was dried over K2CO3 The organic layer was concentrated in vacuo the residue was dissolved in ether filtered the filtrate was washed successively with a 10% NaOH solution and water The organic layer was dried over K2CO3 the solvent was removed in vacuo the residue was diluted with hexane cooled in an ice-bath filtered The filtrate was concentrated in vacuo the residue was distilled at 70°-72° C. (27 mmHg)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl isobutyrimidate hydrochloride (1.8 g, 11.9 mmol) was suspended in hexanes (29.7 mL) and cooled to 0° C. 2,4,6-Collidine (4.1 mL, 30.9 mmol) and ethyl chloroformate (1.9 g, 17.8 mmol) were sequentially added and the mixture was allowed to warm to RT and stirred for 12 h. Organic solvent was removed in vacuo. The residue was suspended in EtOAc (50 mL) and solids were removed by filtration through a pad of diatomaceous earth. The filter cake was washed with EtOAc (3×10 mL) and the combined filtrates were concentrated in vacuo to afford ethyl N-ethoxycarbonylisobutyrimidate (2.2 g, 99%) as a yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6): δ 4.09 (q, J=7.1 Hz, 2H), 4.03 (q, J=7.1 Hz, 2H), 2.65-2.64 (m, 1H), 1.20 (t, J=7.1 Hz, 3H), 1.19 (t, J=7.1 Hz, 3H), 1.07 (d, J=6.8 Hz, 6H). to warm to RT Organic solvent was removed in vacuo solids were removed by filtration through a pad of diatomaceous earth The filter cake was washed with EtOAc (3×10 mL) the combined filtrates were concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isobutyronitrile (1 g, 14.5 mmol) was dissolved in anhydrous ethanol (30 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 isobutyrimidate hydrochloride (1.8 g, 82%) as a colorless solid. 1H NMR (400 MHz, DMSO-d6): δ 11.78 (br s, 1H), 11.05 (br s, 1H), 4.40 (q, J=7.0 Hz, 2H), 2.93-2.92 (m, 1H), 1.33 (t, J=7.0 Hz, 3H), 1.16 (d, J=6.9 Hz, 6H). stirred for 6 h The solvent was removed in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isobutyronitrile (1 g, 14.5 mmol) was dissolved in anhydrous ethanol (30 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 isobutyrimidate hydrochloride (1.8 g, 82%) as a colorless solid. 1H NMR (400 MHz, DMSO-d6): δ 11.78 (br s, 1H), 11.05 (br s, 1H), 4.40 (q, J=7.0 Hz, 2H), 2.93-2.92 (m, 1H), 1.33 (t, J=7.0 Hz, 3H), 1.16 (d, J=6.9 Hz, 6H). stirred for 6 h The solvent was removed in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The method according to claim 1 wherein ethyl isobutyrimidate hydrochloride is neutralized by trimethylamine dissolved in toluene, the free ethyl isobutyrimidate is freed from water by azeotropic distillation; then the dry ethyl isobutyrimidate in toluene is reacted with an excess of diketene dissolved in toluene in the presence of trimethylamine and the resulting organic solution is treated with gaseous ammonia, in molar equivalent amounts and subsequent azeotropic removal of water to form 2-isopropyl-4-methyl-6-hydroxypyrimidine which is dried and recovered from said organic solvent. the free ethyl isobutyrimidate is freed from water by azeotropic distillation then the dry ethyl isobutyrimidate in toluene is reacted with an excess of diketene

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 138.2 g (2 mol) of isobutyronitrile in 101.2 g (2.2 mol) of ethanol cooled to 0° C. was saturated with anhydrous HCl gas (total vol. of HCl=1.5 L: 2.2 mol) at a rate of 1.5 L/min for 35 minutes. The resulting mixture was tightly capped and stored in a refrigerator (-5° C.) for 5 days and then stirred at room temperature for 18 hours. The solid formed was removed by filtration and the filtrate was poured into 2 L of anhydrous ether with stirring and the resulting reaction mixture was stirred at 0°-5° C. for 30 minutes. The precipitated solid was filtered, washed with anhydrous ether, and dried in a vacuum oven (over KOH) to afford 150 g (98.9%) of 1-imino-1-ethoxyisobutane hydrochloride. The resulting mixture was tightly capped The solid formed was removed by filtration the filtrate was poured into 2 L of anhydrous ether with stirring the resulting reaction mixture was stirred at 0°-5° C. for 30 minutes The precipitated solid was filtered washed with anhydrous ether dried in a vacuum oven (over KOH)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 1-imino-1-ethoxyisobutane hydrochloride (610.0 g) in ether (12.5 L) was added ethanol (1940.0 g, 10 mol). The mixture was stirred at 35°-37° C. under N2 for 72 hours. The reaction mixture was filtered, the filtrate was washed with a 10% sodium carbonate solution, followed by a saturated sodium carbonate solution and the organic layer was dried over K2CO3. The organic layer was concentrated in vacuo and the residue was dissolved in ether, filtered and the filtrate was washed successively with a 10% NaOH solution and water. The organic layer was dried over K2CO3, the solvent was removed in vacuo and the residue was diluted with hexane, cooled in an ice-bath and filtered. The filtrate was concentrated in vacuo and the residue was distilled at 70°-72° C. (27 mmHg) to afford 320 g (42%) of 1,1,1-triethoxyisobutane. The reaction mixture was filtered the filtrate was washed with a 10% sodium carbonate solution the organic layer was dried over K2CO3 The organic layer was concentrated in vacuo the residue was dissolved in ether filtered the filtrate was washed successively with a 10% NaOH solution and water The organic layer was dried over K2CO3 the solvent was removed in vacuo the residue was diluted with hexane cooled in an ice-bath filtered The filtrate was concentrated in vacuo the residue was distilled at 70°-72° C. (27 mmHg)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 1-imino-1-ethoxyisobutane hydrochloride (610.0 g) in ether (12.5 L) was added ethanol (1940.0 g, 10 mol). The mixture was stirred at 35°-37° C. under N2 for 72 hours. The reaction mixture was filtered, the filtrate was washed with a 10% sodium carbonate solution, followed by a saturated sodium carbonate solution and the organic layer was dried over K2CO3. The organic layer was concentrated in vacuo and the residue was dissolved in ether, filtered and the filtrate was washed successively with a 10% NaOH solution and water. The organic layer was dried over K2CO3, the solvent was removed in vacuo and the residue was diluted with hexane, cooled in an ice-bath and filtered. The filtrate was concentrated in vacuo and the residue was distilled at 70°-72° C. (27 mmHg) to afford 320 g (42%) of 1,1,1-triethoxyisobutane. The reaction mixture was filtered the filtrate was washed with a 10% sodium carbonate solution the organic layer was dried over K2CO3 The organic layer was concentrated in vacuo the residue was dissolved in ether filtered the filtrate was washed successively with a 10% NaOH solution and water The organic layer was dried over K2CO3 the solvent was removed in vacuo the residue was diluted with hexane cooled in an ice-bath filtered The filtrate was concentrated in vacuo the residue was distilled at 70°-72° C. (27 mmHg)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl isobutyrimidate hydrochloride (1.8 g, 11.9 mmol) was suspended in hexanes (29.7 mL) and cooled to 0° C. 2,4,6-Collidine (4.1 mL, 30.9 mmol) and ethyl chloroformate (1.9 g, 17.8 mmol) were sequentially added and the mixture was allowed to warm to RT and stirred for 12 h. Organic solvent was removed in vacuo. The residue was suspended in EtOAc (50 mL) and solids were removed by filtration through a pad of diatomaceous earth. The filter cake was washed with EtOAc (3×10 mL) and the combined filtrates were concentrated in vacuo to afford ethyl N-ethoxycarbonylisobutyrimidate (2.2 g, 99%) as a yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6): δ 4.09 (q, J=7.1 Hz, 2H), 4.03 (q, J=7.1 Hz, 2H), 2.65-2.64 (m, 1H), 1.20 (t, J=7.1 Hz, 3H), 1.19 (t, J=7.1 Hz, 3H), 1.07 (d, J=6.8 Hz, 6H). to warm to RT Organic solvent was removed in vacuo solids were removed by filtration through a pad of diatomaceous earth The filter cake was washed with EtOAc (3×10 mL) the combined filtrates were concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isobutyronitrile (1 g, 14.5 mmol) was dissolved in anhydrous ethanol (30 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 isobutyrimidate hydrochloride (1.8 g, 82%) as a colorless solid. 1H NMR (400 MHz, DMSO-d6): δ 11.78 (br s, 1H), 11.05 (br s, 1H), 4.40 (q, J=7.0 Hz, 2H), 2.93-2.92 (m, 1H), 1.33 (t, J=7.0 Hz, 3H), 1.16 (d, J=6.9 Hz, 6H). stirred for 6 h The solvent was removed in vacuo