tert-butyl N-[(1R,2R)-2-hydroxycyclopentyl]carbamate

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,2,6,6-Tetramethylpiperidine-N-oxide (2.2 g, 14.2 mmol) and potassium bromide (8.5 g, 71 mmol) are added to a solution of racemic trans-tert-butyl N-[2-hydroxycyclopentyl]carbamate (75 g, 283 mmol) in dichloromethane (285 mL). The mixture is cooled to 5° C. with stirring. A freshly prepared ice cooled (5° C.) sodium hypochlorite aqueous solution (766 mL, 566 mmol, pH adjusted to 7.5-8 by addition of 10 g of solid potassium carbonate) is added with stirring to the reaction mixture while keeping the temperature below 5° C. The mixture is stirred at 5° C. for an additional 30 min. The reaction mixture is diluted with saturated aqueous sodium chloride solution (150 mL). The organic layer is separated and evaporated. The oily red residue is purified over a silica gel pad, eluting with EtOAc/hexanes (1/3) to obtain the title compound as a cream colored solid (43 g, 76%). 1H-NMR (300 MHz, DMSO-d6) δ 6.99 (d, 1H, NH), 3.76 (q, 1H), 1.63-2.31 (m, 6H), 1.37 (s, 9H). is added with stirring to the reaction mixture the temperature below 5° C The mixture is stirred at 5° C. for an additional 30 min The organic layer is separated evaporated The oily red residue is purified over a silica gel pad eluting with EtOAc/hexanes (1/3)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,2,6,6-Tetramethylpiperidine-N-oxide (2.2 g, 14.2 mmol) and potassium bromide (8.5 g, 71 mmol) are added to a solution of racemic trans-tert-butyl N-[2-hydroxycyclopentyl]carbamate (75 g, 283 mmol) in dichloromethane (285 mL). The mixture is cooled to 5° C. with stirring. A freshly prepared ice cooled (5° C.) sodium hypochlorite aqueous solution (766 mL, 566 mmol, pH adjusted to 7.5-8 by addition of 10 g of solid potassium carbonate) is added with stirring to the reaction mixture while keeping the temperature below 5° C. The mixture is stirred at 5° C. for an additional 30 min. The reaction mixture is diluted with saturated aqueous sodium chloride solution (150 mL). The organic layer is separated and evaporated. The oily red residue is purified over a silica gel pad, eluting with EtOAc/hexanes (1/3) to obtain the title compound as a cream colored solid (43 g, 76%). 1H-NMR (300 MHz, DMSO-d6) δ 6.99 (d, 1H, NH), 3.76 (q, 1H), 1.63-2.31 (m, 6H), 1.37 (s, 9H). is added with stirring to the reaction mixture the temperature below 5° C The mixture is stirred at 5° C. for an additional 30 min The organic layer is separated evaporated The oily red residue is purified over a silica gel pad eluting with EtOAc/hexanes (1/3)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,2,6,6-Tetramethylpiperidine-N-oxide (2.2 g, 14.2 mmol) and potassium bromide (8.5 g, 71 mmol) are added to a solution of racemic trans-tert-butyl N-[2-hydroxycyclopentyl]carbamate (75 g, 283 mmol) in dichloromethane (285 mL). The mixture is cooled to 5° C. with stirring. A freshly prepared ice cooled (5° C.) sodium hypochlorite aqueous solution (766 mL, 566 mmol, pH adjusted to 7.5-8 by addition of 10 g of solid potassium carbonate) is added with stirring to the reaction mixture while keeping the temperature below 5° C. The mixture is stirred at 5° C. for an additional 30 min. The reaction mixture is diluted with saturated aqueous sodium chloride solution (150 mL). The organic layer is separated and evaporated. The oily red residue is purified over a silica gel pad, eluting with EtOAc/hexanes (1/3) to obtain the title compound as a cream colored solid (43 g, 76%). 1H-NMR (300 MHz, DMSO-d6) δ 6.99 (d, 1H, NH), 3.76 (q, 1H), 1.63-2.31 (m, 6H), 1.37 (s, 9H). is added with stirring to the reaction mixture the temperature below 5° C The mixture is stirred at 5° C. for an additional 30 min The organic layer is separated evaporated The oily red residue is purified over a silica gel pad eluting with EtOAc/hexanes (1/3)

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

Procedure: To a solution of trans-2-(tert-butoxycarbonyl)aminocyclopentan-1-ol (Prepn. 47, 3.00 g) triphenyl phosphine (5.90 g) and 4-nitrobenzoic acid (2.50 g) in THF (90 mL) was added, at 0° C., diisopropyl azodicarboxylate (4.50 mL). After stirring for 4 h, the solvent was evaporated and the crude product was purified by flash chromatography (SiO2, CH2Cl2:acetone 99:1) to give cis-2-(tert-butoxycarbonyl)amino-1-(4-nitrobenzoyloxy)cyclopentane (3.70 g, 70%). 1H-NMR (300 MHz, DMSO-d6, ppm from TMS): δ 8.33 (2H, d), 8.23 (2H, d), 7.08 (1H, d), 5.25 (1H, m), 3.92 (1H, m), 1.40-2.10 (6H, m), 1.28 (9H, s). the solvent was evaporated the crude product was purified by flash chromatography (SiO2, CH2Cl2:acetone 99:1)

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

Procedure: Dess-Martin periodinane (2.72 g, 6.41 mmol) was added to a stirred solution of tert-butyl 2-hydroxycyclopentylcarbamate (1.23 g, 6.11 mmol, from Step 1) in dichloromethane (30 mL) while the reaction container was placed in a room temperature water bath. After 1.5 h at room temperature, the mixture was quenched with 1 M aqueous sodium thiosulfate. After shaking the mixture vigorously, the dichloromethane phase was separated and concentrated. Silica gel chromatography, eluting with 0 to 50% ethyl acetate in hexanes, gave tert-butyl 2-oxocyclopentylcarbamate as white crystalline solid (824.6 mg, 68% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 5.03 (1 H, br. s.), 3.90 (1 H, br. s.), 2.56 (1 H, br. s.), 2.38 (1 H, dd, J=19.15, 8.80 Hz), 2.08-2.22 (1 H, m), 1.96-2.08 (1 H, m), 1.73-1.89 (1 H, m), 1.52-1.69 (1 H, m), 1.42 (9 H, s). was placed in a room temperature the mixture was quenched with 1 M aqueous sodium thiosulfate the dichloromethane phase was separated concentrated Silica gel chromatography, eluting with 0 to 50% ethyl acetate in hexanes

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,2,6,6-Tetramethylpiperidine-N-oxide (2.2 g, 14.2 mmol) and potassium bromide (8.5 g, 71 mmol) are added to a solution of racemic trans-tert-butyl N-[2-hydroxycyclopentyl]carbamate (75 g, 283 mmol) in dichloromethane (285 mL). The mixture is cooled to 5° C. with stirring. A freshly prepared ice cooled (5° C.) sodium hypochlorite aqueous solution (766 mL, 566 mmol, pH adjusted to 7.5-8 by addition of 10 g of solid potassium carbonate) is added with stirring to the reaction mixture while keeping the temperature below 5° C. The mixture is stirred at 5° C. for an additional 30 min. The reaction mixture is diluted with saturated aqueous sodium chloride solution (150 mL). The organic layer is separated and evaporated. The oily red residue is purified over a silica gel pad, eluting with EtOAc/hexanes (1/3) to obtain the title compound as a cream colored solid (43 g, 76%). 1H-NMR (300 MHz, DMSO-d6) δ 6.99 (d, 1H, NH), 3.76 (q, 1H), 1.63-2.31 (m, 6H), 1.37 (s, 9H). is added with stirring to the reaction mixture the temperature below 5° C The mixture is stirred at 5° C. for an additional 30 min The organic layer is separated evaporated The oily red residue is purified over a silica gel pad eluting with EtOAc/hexanes (1/3)