N-methoxy-N-methyl-1,4-dioxaspiro[4.5]decane-8-carboxamide

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

Procedure: Ethyl 1,4-dioxaspiro[4,5]decane-8-carboxylate (6.28 g, 29.3 mmol) obtained in Step 1 was dissolved in THF, and N,O-dimethylhydroxylamine hydrochloride (4.30 g, 44.1 mmol) was added thereto, followed by stirring. In an atmosphere of argon at −30° C., a 2.0 mol/L solution of isopropylmagnesium chloride in THF (44.1 mL, 88.2 mmol) was added dropwise to the reaction mixture, followed by stirring at −5° C. for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to afford N-methoxy-N-methyl-1,4-dioxaspiro[4,5]decane-8-carboxamide (6.61 g, 99%). by stirring at −5° C. for 1 hour followed by extraction with chloroform The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure The resulting residue was purified through silica gel column chromatography (ethyl acetate)

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

Procedure: To a solution of N-methoxy-N-methyl-1,4-dioxaspiro[4.5]decane-8-carboxamide (1 g, 0.0043 mol) in anhydrous Et2O (20 mL) was added EtMgBr (9 g, 0.043 mol). The reaction mixture was refluxed overnight, and then 200 mL water was added. The mixture was extracted with ethyl acetate. The extract was concentrated and purified by silica gel column chromatography (CH2Cl2:MeOH=150:1) to give the desired product (0.259 g, 26% yield). The reaction mixture was refluxed overnight The mixture was extracted with ethyl acetate The extract was concentrated purified by silica gel column chromatography (CH2Cl2:MeOH=150:1)

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

Procedure: A mixture of N-methoxy-N-methyl-4-oxocyclohexanecarboxamide (2.1 g, 0.114 mol), glycol (0.9 g, 0.136 mol) and toluenesulfonate (0.1 g, cat) in toluene (30 mL) was refluxed overnight and then concentrated. Water was added, and the mixture was extracted with ethyl acetate. The extract was concentrated and purified by silica gel column chromatography (CH2Cl2:MeOH=100:1) to give the desired product (1 g, 38.4% yield). was refluxed overnight concentrated Water was added the mixture was extracted with ethyl acetate The extract was concentrated purified by silica gel column chromatography (CH2Cl2:MeOH=100:1)

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

Procedure: Ethyl 1,4-dioxaspiro[4,5]decane-8-carboxylate (6.28 g, 29.3 mmol) obtained in Step 1 was dissolved in THF, and N,O-dimethylhydroxylamine hydrochloride (4.30 g, 44.1 mmol) was added thereto, followed by stirring. In an atmosphere of argon at −30° C., a 2.0 mol/L solution of isopropylmagnesium chloride in THF (44.1 mL, 88.2 mmol) was added dropwise to the reaction mixture, followed by stirring at −5° C. for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to afford N-methoxy-N-methyl-1,4-dioxaspiro[4,5]decane-8-carboxamide (6.61 g, 99%). by stirring at −5° C. for 1 hour followed by extraction with chloroform The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure The resulting residue was purified through silica gel column chromatography (ethyl acetate)

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

Procedure: Ethyl 1,4-dioxaspiro[4,5]decane-8-carboxylate (6.28 g, 29.3 mmol) obtained in Step 1 was dissolved in THF, and N,O-dimethylhydroxylamine hydrochloride (4.30 g, 44.1 mmol) was added thereto, followed by stirring. In an atmosphere of argon at −30° C., a 2.0 mol/L solution of isopropylmagnesium chloride in THF (44.1 mL, 88.2 mmol) was added dropwise to the reaction mixture, followed by stirring at −5° C. for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to afford N-methoxy-N-methyl-1,4-dioxaspiro[4,5]decane-8-carboxamide (6.61 g, 99%). by stirring at −5° C. for 1 hour followed by extraction with chloroform The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure The resulting residue was purified through silica gel column chromatography (ethyl acetate)

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

Procedure: Ethyl 1,4-dioxaspiro[4,5]decane-8′-carboxylate (6.28 g, 29.3 mmol) obtained in Step 1 was dissolved in THF, and N,O-dimethylhydroxylamine hydrochloride (4.30 g, 44.1 mmol) was added thereto, followed by stirring. In an atmosphere of argon at −30° C., a 2.0 mol/L solution of isopropylmagnesium chloride in THF (44.1 mL, 88.2 mmol) was added dropwise to the reaction mixture, followed by stirring at −5° C. for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to afford N-methoxy-N-methyl-1,4-dioxaspiro[4,5]decane-8-carboxamide (6.61 g, 99%). by stirring at −5° C. for 1 hour followed by extraction with chloroform The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure The resulting residue was purified through silica gel column chromatography (ethyl acetate)

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

Procedure: Ethyl 1,4-dioxaspiro[4,5]decane-8′-carboxylate (6.28 g, 29.3 mmol) obtained in Step 1 was dissolved in THF, and N,O-dimethylhydroxylamine hydrochloride (4.30 g, 44.1 mmol) was added thereto, followed by stirring. In an atmosphere of argon at −30° C., a 2.0 mol/L solution of isopropylmagnesium chloride in THF (44.1 mL, 88.2 mmol) was added dropwise to the reaction mixture, followed by stirring at −5° C. for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to afford N-methoxy-N-methyl-1,4-dioxaspiro[4,5]decane-8-carboxamide (6.61 g, 99%). by stirring at −5° C. for 1 hour followed by extraction with chloroform The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure The resulting residue was purified through silica gel column chromatography (ethyl acetate)

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

Procedure: Ethyl 1,4-dioxaspiro[4,5]decane-8-carboxylate (6.28 g, 29.3 mmol) obtained in Step 1 was dissolved in THF, and N,O-dimethylhydroxylamine hydrochloride (4.30 g, 44.1 mmol) was added thereto, followed by stirring. In an atmosphere of argon at −30° C., a 2.0 mol/L solution of isopropylmagnesium chloride in THF (44.1 mL, 88.2 mmol) was added dropwise to the reaction mixture, followed by stirring at −5° C. for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to afford N-methoxy-N-methyl-1,4-dioxaspiro[4,5]decane-8-carboxamide (6.61 g, 99%). by stirring at −5° C. for 1 hour followed by extraction with chloroform The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure The resulting residue was purified through silica gel column chromatography (ethyl acetate)

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

Procedure: Ethyl 1,4-dioxaspiro[4,5]decane-8-carboxylate (6.28 g, 29.3 mmol) obtained in Step 1 was dissolved in THF, and N,O-dimethylhydroxylamine hydrochloride (4.30 g, 44.1 mmol) was added thereto, followed by stirring. In an atmosphere of argon at −30° C., a 2.0 mol/L solution of isopropylmagnesium chloride in THF (44.1 mL, 88.2 mmol) was added dropwise to the reaction mixture, followed by stirring at −5° C. for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to afford N-methoxy-N-methyl-1,4-dioxaspiro[4,5]decane-8-carboxamide (6.61 g, 99%). by stirring at −5° C. for 1 hour followed by extraction with chloroform The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure The resulting residue was purified through silica gel column chromatography (ethyl acetate)

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

Procedure: To a solution of N-methoxy-N-methyl-1,4-dioxaspiro[4.5]decane-8-carboxamide (1 g, 0.0043 mol) in anhydrous Et2O (20 mL) was added EtMgBr (9 g, 0.043 mol). The reaction mixture was refluxed overnight, and then 200 mL water was added. The mixture was extracted with ethyl acetate. The extract was concentrated and purified by silica gel column chromatography (CH2Cl2:MeOH=150:1) to give the desired product (0.259 g, 26% yield). The reaction mixture was refluxed overnight The mixture was extracted with ethyl acetate The extract was concentrated purified by silica gel column chromatography (CH2Cl2:MeOH=150:1)

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

Procedure: A mixture of N-methoxy-N-methyl-4-oxocyclohexanecarboxamide (2.1 g, 0.114 mol), glycol (0.9 g, 0.136 mol) and toluenesulfonate (0.1 g, cat) in toluene (30 mL) was refluxed overnight and then concentrated. Water was added, and the mixture was extracted with ethyl acetate. The extract was concentrated and purified by silica gel column chromatography (CH2Cl2:MeOH=100:1) to give the desired product (1 g, 38.4% yield). was refluxed overnight concentrated Water was added the mixture was extracted with ethyl acetate The extract was concentrated purified by silica gel column chromatography (CH2Cl2:MeOH=100:1)

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

Procedure: Ethyl 1,4-dioxaspiro[4,5]decane-8-carboxylate (6.28 g, 29.3 mmol) obtained in Step 1 was dissolved in THF, and N,O-dimethylhydroxylamine hydrochloride (4.30 g, 44.1 mmol) was added thereto, followed by stirring. In an atmosphere of argon at −30° C., a 2.0 mol/L solution of isopropylmagnesium chloride in THF (44.1 mL, 88.2 mmol) was added dropwise to the reaction mixture, followed by stirring at −5° C. for 1 hour. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (ethyl acetate) to afford N-methoxy-N-methyl-1,4-dioxaspiro[4,5]decane-8-carboxamide (6.61 g, 99%). by stirring at −5° C. for 1 hour followed by extraction with chloroform The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure The resulting residue was purified through silica gel column chromatography (ethyl acetate)