tert-butyl 2-(1-hydroxyethyl)pyrrolidine-1-carboxylate

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

Procedure: 2-(1-Hydroxy-ethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 4.3 mmol) in N,N-dimethylformamide (15 mL) is cooled to 0° C., MeI (1 mL) is added followed by NaH (380 mg, 60% suspension in mineral oil, 9.5 mmol). The resulting mixture is allowed to stir at room temperature for 2 hours until TLC reported no remaining starting material. The reaction is quenched with ice and ether is added. N,N-dimethylformamide is washed away with H2O and the ether layer is dried and concentrated to afford the crude product used directly in the next step. The reaction is quenched with ice and ether is added N,N-dimethylformamide is washed away with H2O the ether layer is dried concentrated

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

Procedure: 2-(1-Hydroxy-ethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 4.3 mmol) in N,N-dimethylformamide (15 mL) is cooled to 0° C., MeI (1 mL) is added followed by NaH (380 mg, 60% suspension in mineral oil, 9.5 mmol). The resulting mixture is allowed to stir at room temperature for 2 hours until TLC reported no remaining starting material. The reaction is quenched with ice and ether is added. N,N-dimethylformamide is washed away with H2O and the ether layer is dried and concentrated to afford the crude product used directly in the next step. The reaction is quenched with ice and ether is added N,N-dimethylformamide is washed away with H2O the ether layer is dried concentrated

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

Procedure: 2-(1-Hydroxy-ethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 4.3 mmol) in N,N-dimethylformamide (15 mL) is cooled to 0° C., MeI (1 mL) is added followed by NaH (380 mg, 60% suspension in mineral oil, 9.5 mmol). The resulting mixture is allowed to stir at room temperature for 2 hours until TLC reported no remaining starting material. The reaction is quenched with ice and ether is added. N,N-dimethylformamide is washed away with H2O and the ether layer is dried and concentrated to afford the crude product used directly in the next step. The reaction is quenched with ice and ether is added N,N-dimethylformamide is washed away with H2O the ether layer is dried concentrated

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

Procedure: 2-(1-Hydroxy-ethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 4.6 mmol) in CH2Cl2 is cooled to 0° C. and TFA (2.5 mL) is added dropwise. The mixture is allowed to stir at room temperature overnight. All the volatiles were removed and CH3CN (20 mL) is added. After addition of 4-nitrobenzyl bromide (1.25 g, 5.78 mmol) and K2CO3 (2.0 g, 14.4 mmol), the mixture is stirred at room temperature for 5 hours. All the volatiles were removed CH3CN (20 mL) is added the mixture is stirred at room temperature for 5 hours

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

Procedure: 2-(1-Hydroxy-ethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 4.6 mmol) in CH2Cl2 is cooled to 0° C. and TFA (2.5 mL) is added dropwise. The mixture is allowed to stir at room temperature overnight. All the volatiles were removed and CH3CN (20 mL) is added. After addition of 4-nitrobenzyl bromide (1.25 g, 5.78 mmol) and K2CO3 (2.0 g, 14.4 mmol), the mixture is stirred at room temperature for 5 hours. All the volatiles were removed CH3CN (20 mL) is added the mixture is stirred at room temperature for 5 hours

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

Procedure: To a mixture of tert-butyl 2-(1-hydroxyethyl)pyrrolidine-1-carboxylate (750 mg, 3.48 mmol) in DMF (12 mL) at 0° C. was added methyl iodide (0.75 mL, 11.98 mmol) followed by sodium hydride (184 mg, 7.66 mmol). The mixture was stirred for 2 hours at room temperature. The reaction was quenched with ice and diluted with diethyl ether. The organic layer was washed with water and brine, dried over sodium sulfate, and filtered and concentrated under reduced pressure to afford tert-butyl 2-(1-methoxyethyl)pyrrolidine-1-carboxylate. 1H NMR (500 MHz, CDCl3) δ 3.92-3.45 (m, 2H), 3.45-3.23 (m, 4H), 2.11-1.66 (m, 4H), 1.63 (s, 1H), 1.46 (s, 9H), 1.04 (dd, J=6.3, 30.8, 3H). The reaction was quenched with ice diluted with diethyl ether The organic layer was washed with water and brine dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: To a mixture of tert-butyl 2-(1-hydroxyethyl)pyrrolidine-1-carboxylate (750 mg, 3.48 mmol) in DMF (12 mL) at 0° C. was added methyl iodide (0.75 mL, 11.98 mmol) followed by sodium hydride (184 mg, 7.66 mmol). The mixture was stirred for 2 hours at room temperature. The reaction was quenched with ice and diluted with diethyl ether. The organic layer was washed with water and brine, dried over sodium sulfate, and filtered and concentrated under reduced pressure to afford tert-butyl 2-(1-methoxyethyl)pyrrolidine-1-carboxylate. 1H NMR (500 MHz, CDCl3) δ 3.92-3.45 (m, 2H), 3.45-3.23 (m, 4H), 2.11-1.66 (m, 4H), 1.63 (s, 1H), 1.46 (s, 9H), 1.04 (dd, J=6.3, 30.8, 3H). The reaction was quenched with ice diluted with diethyl ether The organic layer was washed with water and brine dried over sodium sulfate filtered concentrated under reduced pressure