tert-butyl N-(2-hydroxy-2-methylcyclopentyl)carbamate

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

Procedure: To a solution of tert-butyl-2-hydroxy-2-methyl-cyclopentylcarbamate (25 g, 104.5 mmol) in dichloromethane (210 mL) is added hydrogen chloride in dioxane (156 mL, 6 mol, 4 M) and the reaction is stirred at room temperature for 3 h. The solvent is evaporated and the resulting material is dried under vacuum to a constant weight to obtain the title compound (20.4 g) as a dark brown oil which is used in the next step without further purification. GC-MS 115.1 (M+); GC-MS analysis shows a cis/trans mixture in about a 3/2 ratio. The solvent is evaporated the resulting material is dried under vacuum to a constant weight

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

Procedure: To a solution of tert-butyl-2-hydroxy-2-methyl-cyclopentylcarbamate (25 g, 104.5 mmol) in dichloromethane (210 mL) is added hydrogen chloride in dioxane (156 mL, 6 mol, 4 M) and the reaction is stirred at room temperature for 3 h. The solvent is evaporated and the resulting material is dried under vacuum to a constant weight to obtain the title compound (20.4 g) as a dark brown oil which is used in the next step without further purification. GC-MS 115.1 (M+); GC-MS analysis shows a cis/trans mixture in about a 3/2 ratio. The solvent is evaporated the resulting material is dried under vacuum to a constant weight

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

Procedure: To a solution of tert-butyl-2-hydroxy-2-methyl-cyclopentylcarbamate (25 g, 104.5 mmol) in dichloromethane (210 mL) is added hydrogen chloride in dioxane (156 mL, 6 mol, 4 M) and the reaction is stirred at room temperature for 3 h. The solvent is evaporated and the resulting material is dried under vacuum to a constant weight to obtain the title compound (20.4 g) as a dark brown oil which is used in the next step without further purification. GC-MS 115.1 (M+); GC-MS analysis shows a cis/trans mixture in about a 3/2 ratio. The solvent is evaporated the resulting material is dried under vacuum to a constant weight

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

Procedure: (Diethylamino)sulphur trifluoride (2.75 mL, 20.84 mmol) was added to a solution of tert-butyl 2-hydroxy-2-methylcyclopentylcarbamate (2.243 g, 10.42 mmol, from Step 3) in dichloromethane (40 mL) at −78° C. under nitrogen. After 4 h at −78° C., the mixture was quenched with saturated sodium bicarbonate, allowed to warm to room temperature, and extracted with dichloromethane. The dichloromethane phase was concentrated and purified by silica gel chromatography, eluting with 0 to 50% ethyl acetate in hexanes, to give tert-butyl 2-fluoro-2-methylcyclopentylcarbamate as brown oil (1.095 g, 48% yield). 1H NMR analysis indicated approximately 3.5:1 mixture of two diastereomers. the mixture was quenched with saturated sodium bicarbonate extracted with dichloromethane The dichloromethane phase was concentrated purified by silica gel chromatography eluting with 0 to 50% ethyl acetate in hexanes

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

Procedure: A 1.6 M ether solution of methyllithium (13.59 mL, 21.75 mmol) was added to a stirred suspension of tert-butyl 2-oxocyclopentylcarbamate (1.97 g, 9.89 mmol, from Step 2) and cerium(III) chloride (5.36 g, 21.75 mmol) in tetrahydrofuran (50 mL) at −78° C. under nitrogen. After 2.5 h at −78° C., the mixture was quenched with saturated ammonium chloride, allowed to warm to room temperature, and filtered through a short bed of Celite to remove insoluble cerium salt. The filter cake was rinsed with ethyl acetate. The filtrated was extracted with ethyl acetate three times. The combined ethyl acetate phase was washed with saturated ammonium chloride and brine respectively, dried (MgSO4), filtered and concentrated. Silica gel chromatography, eluting with 0 to 50% ethyl acetate in hexanes, gave tert-butyl 2-hydroxy-2-methylcyclopentylcarbamate as yellow solid (1.47 g, 82% yield). 1H NMR analysis indicated the presence of approximately a 3:1 diastereomeric mixture. the mixture was quenched with saturated ammonium chloride filtered through a short bed of Celite to remove insoluble cerium salt The filter cake was rinsed with ethyl acetate The filtrated was extracted with ethyl acetate three times The combined ethyl acetate phase was washed with saturated ammonium chloride and brine respectively dried (MgSO4) filtered concentrated Silica gel chromatography, eluting with 0 to 50% ethyl acetate in hexanes

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

Procedure: To a solution of tert-butyl-2-hydroxy-2-methyl-cyclopentylcarbamate (25 g, 104.5 mmol) in dichloromethane (210 mL) is added hydrogen chloride in dioxane (156 mL, 6 mol, 4 M) and the reaction is stirred at room temperature for 3 h. The solvent is evaporated and the resulting material is dried under vacuum to a constant weight to obtain the title compound (20.4 g) as a dark brown oil which is used in the next step without further purification. GC-MS 115.1 (M+); GC-MS analysis shows a cis/trans mixture in about a 3/2 ratio. The solvent is evaporated the resulting material is dried under vacuum to a constant weight