tert-butyl 1-oxa-9-azaspiro[5.5]undec-3-ene-9-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of Example 518B (0.79 g, 2.81 mmol) in degassed benzene (100 mL) at room temperature was treated with bis-tricyclohexylphosphine benzylidene ruthenium (IV) dichloride (150 mg), stirred for 18 hours, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 10%-25% ethyl acetate/heptane to provide the desired product. MS (DCI(+)) m/e 254 (M+H)+. concentrated The concentrate was purified by flash column chromatography on silica gel with 10%-25% ethyl acetate/heptane

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

Procedure: Borane tetrahydrofuran complex (1M in tetrahydrofuran, 23.68 mL, 23.68 mmol) was added dropwise to a solution of 1,1-dimethylethyl 1-oxa-9-azaspiro[5.5]undec-3-en-9-carboxylate (Description 131, 2.0 g, 7.89 mmol) in tetrahydrofuran (30 mL) and the mixture was stirred at room temperature for 6.5 hours. Water (25 mL), aqueous sodium hydroxide (4M, 25 mL) and hydrogen peroxide (37%, 25 mL) were added and the mixture was stirred at room temperature for 20 minutes. Water (100 mL) and diethyl ether (100 mL) were added and the layers were separated. The aqueous fraction was extracted with diethyl ether (100 mL) and the combined organic fractions were washed with brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate. The residue was purified by MPLC on silica gel, eluting with ethyl acetate, to give 1,1-dimethylethyl 3-hydroxy-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate (520 mg, 24%); 1H NMR (360 MHz, CDCl3) δ 3.76–3.71 (4H, m), 3.50–3.45 (1H, m), 3.16–3.07 (2H, m), 1.92–1.85 (3H, m), 1.75–1.63 (2H, m), 1.46 (9H, s), and 1.45–1.35 (3H, m); and 1,1-dimethylethyl 4-hydroxy-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate (200 mg, 9%);. 1H NMR (400 MHz, CDCl3) δ 4.02–3.93 (1H, m), 3.87–3.83 (1H, m), 3.75–3.71 (2H, m), 3.57 (1H, dt, J 2.3, 11.7 Hz), 3.19 (1H, t, J 11.3 Hz), 3.03 (1H, t, J 11.7 Hz), 1.95–1.87 (2H, m), 1.86–1.81 (1H, m), 1.68–1.65 (1H, m), 1.57–1.47 (2H, m), 1.45 (9H, s), and 1.41–1.28 (2H, m). the mixture was stirred at room temperature for 20 minutes the layers were separated The aqueous fraction was extracted with diethyl ether (100 mL) the combined organic fractions were washed with brine dried (MgSO4) the solvent was evaporated under reduced pressure The residue was purified by flash column chromatography on silica gel eluting with ethyl acetate The residue was purified by MPLC on silica gel eluting with ethyl acetate

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

Procedure: Borane tetrahydrofuran complex (1M in tetrahydrofuran, 23.68 mL, 23.68 mmol) was added dropwise to a solution of 1,1-dimethylethyl 1-oxa-9-azaspiro[5.5]undec-3-en-9-carboxylate (Description 131, 2.0 g, 7.89 mmol) in tetrahydrofuran (30 mL) and the mixture was stirred at room temperature for 6.5 hours. Water (25 mL), aqueous sodium hydroxide (4M, 25 mL) and hydrogen peroxide (37%, 25 mL) were added and the mixture was stirred at room temperature for 20 minutes. Water (100 mL) and diethyl ether (100 mL) were added and the layers were separated. The aqueous fraction was extracted with diethyl ether (100 mL) and the combined organic fractions were washed with brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate. The residue was purified by MPLC on silica gel, eluting with ethyl acetate, to give 1,1-dimethylethyl 3-hydroxy-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate (520 mg, 24%); 1H NMR (360 MHz, CDCl3) δ 3.76–3.71 (4H, m), 3.50–3.45 (1H, m), 3.16–3.07 (2H, m), 1.92–1.85 (3H, m), 1.75–1.63 (2H, m), 1.46 (9H, s), and 1.45–1.35 (3H, m); and 1,1-dimethylethyl 4-hydroxy-1-oxa-9-azaspiro[5.5]undecane-9-carboxylate (200 mg, 9%);. 1H NMR (400 MHz, CDCl3) δ 4.02–3.93 (1H, m), 3.87–3.83 (1H, m), 3.75–3.71 (2H, m), 3.57 (1H, dt, J 2.3, 11.7 Hz), 3.19 (1H, t, J 11.3 Hz), 3.03 (1H, t, J 11.7 Hz), 1.95–1.87 (2H, m), 1.86–1.81 (1H, m), 1.68–1.65 (1H, m), 1.57–1.47 (2H, m), 1.45 (9H, s), and 1.41–1.28 (2H, m). the mixture was stirred at room temperature for 20 minutes the layers were separated The aqueous fraction was extracted with diethyl ether (100 mL) the combined organic fractions were washed with brine dried (MgSO4) the solvent was evaporated under reduced pressure The residue was purified by flash column chromatography on silica gel eluting with ethyl acetate The residue was purified by MPLC on silica gel eluting with ethyl acetate

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

Procedure: Solutions of 1,1-dimethylethyl 4-(2-propenyl)-4-(2-propenyloxy)-1-piperidinecarboxylate (Description 130, 4.9 g, 17.4 mmol) in dichloromethane (1.2 L) and bis(tricyclohexylphosphine)benzylidine ruthenium (IV) dichloride (717 mg, 0.87 mmol) in dichloromethane (1.2 L) were added dropwise simultaneously to dichloromethane (600 mL) over a period of 8 hours, and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography on silica gel, eluting with 9:1 isohexane:ethyl acetate, to give the title compound (3.3 g, 75%). m/z (ES+) 254 (M+1). The solvent was evaporated under reduced pressure the residue was purified by flash column chromatography on silica gel eluting with 9:1 isohexane

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

Procedure: Solutions of 1,1-dimethylethyl 4-(2-propenyl)-4-(2-propenyloxy)-1-piperidinecarboxylate (Description 130, 4.9 g, 17.4 mmol) in dichloromethane (1.2 L) and bis(tricyclohexylphosphine)benzylidine ruthenium (IV) dichloride (717 mg, 0.87 mmol) in dichloromethane (1.2 L) were added dropwise simultaneously to dichloromethane (600 mL) over a period of 8 hours, and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography on silica gel, eluting with 9:1 isohexane:ethyl acetate, to give the title compound (3.3 g, 75%). m/z (ES+) 254 (M+1). The solvent was evaporated under reduced pressure the residue was purified by flash column chromatography on silica gel eluting with 9:1 isohexane

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

Procedure: Solutions of 1,1-dimethylethyl 4-(2-propenyl)-4-(2-propenyloxy)-1-piperidinecarboxylate (Description 130, 4.9 g, 17.4 mmol) in dichloromethane (1.2 L) and bis(tricyclohexylphosphine)benzylidine ruthenium (IV) dichloride (717 mg, 0.87 mmol) in dichloromethane (1.2 L) were added dropwise simultaneously to dichloromethane (600 mL) over a period of 8 hours, and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography on silica gel, eluting with 9:1 isohexane:ethyl acetate, to give the title compound (3.3 g, 75%). m/z (ES+) 254 (M+1). The solvent was evaporated under reduced pressure the residue was purified by flash column chromatography on silica gel eluting with 9:1 isohexane

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

Procedure: A solution of Example 518B (0.79 g, 2.81 mmol) in degassed benzene (100 mL) at room temperature was treated with bis-tricyclohexylphosphine benzylidene ruthenium (IV) dichloride (150 mg), stirred for 18 hours, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 10%-25% ethyl acetate/heptane to provide the desired product. MS (DCI(+)) m/e 254 (M+H)+. concentrated The concentrate was purified by flash column chromatography on silica gel with 10%-25% ethyl acetate/heptane

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

Procedure: A solution of Example 518B (0.79 g, 2.81 mmol) in degassed benzene (100 mL) at room temperature was treated with bis-tricyclohexylphosphine benzylidene ruthenium (IV) dichloride (150 mg), stirred for 18 hours, and concentrated The concentrate was purified by flash column chromatography on silica gel with 10%-25% ethyl acetate/heptane to provide the desired product. MS (DCI(+)) m/e 254 (M+H)+. concentrated The concentrate was purified by flash column chromatography on silica gel with 10%-25% ethyl acetate/heptane