2-(氨乙基)-2-甲基-1,3-二氧戊环

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Fluoro-2-methyl-benzaldehyde (4 g) was added to a solution of 4-aminobutan-2-one ethylene acetal (3.8 g) in dry benzene (50 mL) and the solution was stirred at r.t. under a nitrogen atmosphere. After 1 hour the mixture was heated at reflux for 16 hours and then allowed to cool to r.t. This solution was slowly added to a refluxing solution of p-toluenesulphonic acid (10.6 g) in dry benzene (50 mL) previously refluxed for 1 hour with a Dean-Stark apparatus. After 3.5 hours the crude solution was cooled and made basic with a saturated potassium carbonate solution and taken up with AcOEt (50 mL). The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL). The organic layer was dried and concentrated in vacuo to a yellow thick oil as residue (7.23 g). A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) and stirred at 60° C. for 16 hours. The solution was basified with solid potassium carbonate and extracted with DCM (5×50 mL). The combined organic phases were washed with brine (50 mL), dried and concentrated in vacuo to give the title compound (2.5 g) as a thick yellow oil. After 1 hour the mixture was heated at reflux for 16 hours to cool to r.t previously refluxed for 1 hour with a Dean-Stark apparatus The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL) The organic layer was dried concentrated in vacuo to a yellow thick oil as residue (7.23 g) A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) stirred at 60° C. for 16 hours extracted with DCM (5×50 mL) The combined organic phases were washed with brine (50 mL) dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Methyl-4-fluoro-benzaldehyde (4 g) was added to a solution of 4-aminobutan-2-one ethylene acetal (3.8 g) in dry benzene (50 mL) and the solution was stirred at r.t. under a nitrogen atmosphere. After 1 hour the mixture was heated at reflux for 16 hours and then allowed to cool to r.t. This solution was slowly added to a refluxing solution of p-toluensulphonic acid (10.6 g) in dry benzene (50 mL) previously refluxed for 1 hour with a Dean-Stark apparatus. After 3.5 hours the crude solution was cooled and made basic with a saturated potassium carbonate solution and taken up with AcOEt (50 mL). The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL). The organic layer was dried and concentrated in vacuo to a yellow thick oil as residue (7.23 g). A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) and stirred at 60° C. for 16 hours. The solution was basified with solid potassium carbonate and extracted with DCM (5×50 mL). The combined organic phases were washed with brine (50 mL), dried and concentrated in vacuo to give the title compound (2.5 g) as a thick yellow oil. After 1 hour the mixture was heated at reflux for 16 hours to cool to r.t previously refluxed for 1 hour with a Dean-Stark apparatus The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL) The organic layer was dried concentrated in vacuo to a yellow thick oil as residue (7.23 g) A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) stirred at 60° C. for 16 hours extracted with DCM (5×50 mL) The combined organic phases were washed with brine (50 mL) dried concentrated in vacuo

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of benzaldehyde (10.6 g) and 2-methyl-1,3-dioxolane-2-ethanamine (13.1 g) in toluene (100 ml) was stirred for 16 hours at RT. This solution was added at 100° C. to a solution of 4-methylbenzenesulfonic acid (34.4 g) in toluene (100 ml) and the mixture was stirred for 1 hour at 100° C. The mixture was poured into an ice/water bath, K2CO3 was added to a pH of about 8 and extracted with ethyl acetate. The organic layer was dried, filtered and the solvent evaporated, yielding 14.3 g (70%) of (±)-7-phenyl-1,3-dioxa-8-azaspiro[4.5]decane (interm. 11). The mixture was poured into an ice/water bath extracted with ethyl acetate The organic layer was dried filtered the solvent evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Methyl-4-fluoro-benzaldehyde (4 g) was added to a solution of 4-aminobutan-2-one ethylene acetal (3.8 g) in dry benzene (50 mL) and the solution was stirred at r.t. under a nitrogen atmosphere. After 1 hour the mixture was heated at reflux for 16 hours and then allowed to cool to r.t. This solution was slowly added to a refluxing solution of p-toluensulphonic acid (10.6 g) in dry benzene (50 mL) previously refluxed for 1 hour with a Dean-Stark apparatus. After 3.5 hours the crude solution was cooled and made basic with a saturated potassium carbonate solution and taken up with AcOEt (50 mL). The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL). The organic layer was dried and concentrated in vacuo to a yellow thick oil as residue (7.23 g). A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) and stirred at 60° C. for 16 hours. The solution was basified with solid potassium carbonate and extracted with DCM (5×50 mL). The combined organic phases were washed with brine (50 mL), dried and concentrated in vacuo to give the title compound (2.5 g) as a thick yellow oil. After 1 hour the mixture was heated at reflux for 16 hours to cool to r.t previously refluxed for 1 hour with a Dean-Stark apparatus The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL) The organic layer was dried concentrated in vacuo to a yellow thick oil as residue (7.23 g) A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) stirred at 60° C. for 16 hours extracted with DCM (5×50 mL) The combined organic phases were washed with brine (50 mL) dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Methyl-4-fluoro-benzaldehyde (4 g) was added to a solution of 4-aminobutan-2-one ethylene acetal (3.8 g) in dry benzene (50 mL) and the solution was stirred at r.t. under a nitrogen atmosphere. After 1 hour the mixture was heated at reflux for 16 hours and then allowed to cool to r.t. This solution was slowly added to a refluxing solution of p-toluensulphonic acid (10.6 g) in dry benzene (50 mL) previously refluxed for 1 hour with a Dean-Stark apparatus. After 3.5 hours the crude solution was cooled and made basic with a saturated potassium carbonate solution and taken up with AcOEt (50 mL). The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL). The organic layer was dried and concentrated in vacuo to a yellow thick oil as residue (7.23 g). A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) and stirred at 60° C. for 16 hours. The solution was basified with solid potassium carbonate and extracted with DCM (5×50 mL). The combined organic phases were washed with brine (50 mL), dried and concentrated in vacuo to give the title compound (2.5 g) as a thick yellow oil. After 1 hour the mixture was heated at reflux for 16 hours to cool to r.t previously refluxed for 1 hour with a Dean-Stark apparatus The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL) The organic layer was dried concentrated in vacuo to a yellow thick oil as residue (7.23 g) A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) stirred at 60° C. for 16 hours extracted with DCM (5×50 mL) The combined organic phases were washed with brine (50 mL) dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Fluoro-4-methyl-benzaldehyde (4 g) was added to a solution of 4-aminobutan-2-one ethylene acetal (3.8 g) in dry benzene (50 mL) and the solution was stirred at r.t. under a nitrogen atmosphere. After 1 hour the mixture was heated at reflux for 16 hours and then allowed to cool to r.t. This solution was slowly added to a refluxing solution of p-toluenesulphonic acid (10.6 g) in dry benzene (50 mL) previously refluxed for 1 hour with a Dean-Stark apparatus. After 3.5 hours the crude solution was cooled and made basic with a saturated potassium carbonate solution and taken up with AcOEt (50 mL). The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL). The organic layer was dried and concentrated in vacuo to a yellow thick oil as residue (7.23 g). A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) and stirred at 60° C. for 16 hours. The solution was basified with solid potassium carbonate and extracted with DCM (5×50 mL). The combined organic phases were washed with brine (50 mL), dried and concentrated in vacuo to give the title compound (2.5 g) as a thick yellow oil. After 1 hour the mixture was heated at reflux for 16 hours to cool to r.t previously refluxed for 1 hour with a Dean-Stark apparatus The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL) The organic layer was dried concentrated in vacuo to a yellow thick oil as residue (7.23 g) A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) stirred at 60° C. for 16 hours extracted with DCM (5×50 mL) The combined organic phases were washed with brine (50 mL) dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2-Methyl-4-fluoro-benzaldehyde (4 g) was added to a solution of 4-aminobutan-2-one ethylene acetal (3.8 g) in dry benzene (50 mL) and the solution was stirred at r.t. under a nitrogen atmosphere. After 1 hour the mixture was heated at reflux for 16 hours and then allowed to cool to r.t. This solution was slowly added to a refluxing solution of p-toluensulphonic acid (10.6 g) in dry benzene (50 mL) previously refluxed for 1 hour with a Dean-Stark apparatus. After 3.5 hours the crude solution was cooled and made basic with a saturated potassium carbonate solution and taken up with AcOEt (50 mL). The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL). The organic layer was dried and concentrated in vacuo to a yellow thick oil as residue (7.23 g). A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) and stirred at 60° C. for 16 hours. The solution was basified with solid potassium carbonate and extracted with DCM (5×50 mL). The combined organic phases were washed with brine (50 mL), dried and concentrated in vacuo to give the title compound (2.5 g) as a thick yellow oil. After 1 hour the mixture was heated at reflux for 16 hours to cool to r.t previously refluxed for 1 hour with a Dean-Stark apparatus The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL) The organic layer was dried concentrated in vacuo to a yellow thick oil as residue (7.23 g) A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) stirred at 60° C. for 16 hours extracted with DCM (5×50 mL) The combined organic phases were washed with brine (50 mL) dried concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Fluoro-2-methyl-benzaldehyde (4 g) was added to a solution of 4-aminobutan-2-one ethylene acetal (3.8 g) in dry benzene (50 mL) and the solution was stirred at r.t. under a nitrogen atmosphere. After 1 hour the mixture was heated at reflux for 16 hours and then allowed to cool to r.t. This solution was slowly added to a refluxing solution of p-toluensulphonic acid (10.6 g) in dry benzene (50 mL) previously refluxed for 1 hour with a Dean-Stark apparatus. After 3.5 hours the crude solution was cooled and made basic with a saturated potassium carbonate solution and taken up with AcOEt (50 mL). The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL). The organic layer was dried and concentrated in vacuo to a yellow thick oil as residue (7.23 g). A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) and stirred at 60° C. for 16 hours. The solution was basified with solid potassium carbonate and extracted with DCM (5×50 mL). The combined organic phases were washed with brine (50 mL), dried and concentrated in vacuo to give the title compound (2.5 g) as a thick yellow oil. After 1 hour the mixture was heated at reflux for 16 hours to cool to r.t previously refluxed for 1 hour with a Dean-Stark apparatus The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL) The organic layer was dried concentrated in vacuo to a yellow thick oil as residue (7.23 g) A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) stirred at 60° C. for 16 hours extracted with DCM (5×50 mL) The combined organic phases were washed with brine (50 mL) dried concentrated in vacuo