ethyl (2S)-pyrrolidine-2-carboxylate;hydrochloride

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

Procedure: 1.8 g (0.01 mol) of proline ethyl ester hydrochloride and 1.0 g of triethylamine were added dropwise to 30 ml of benzene and 2.6 g (0.01 mol) of 4-chloro-3-isopropoxycarbonylphenyl isothiocyanate were added thereto. The mixture was stirred at room temperature for an hour, washed with water, dried over anhydrous sodium sulfate, and then concentrated. The residue was purified by means of silica gel column chromatography to give 2.5 g (yield 63%) of the desired product as a yellow glassy substance. were added washed with water dried over anhydrous sodium sulfate concentrated The residue was purified by means of silica gel column chromatography

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

Procedure: A mixture of (S)-1-tert-butyl 2-ethyl pyrrolidine-1,2-dicarboxylate (200 mg, 0.822 mmol) and HCl in 1,4-dioxane (4110 μl, 16.44 mmol) was allowed to stir for 1 hour. The reaction mixture was concentrated to give (S)-ethyl pyrrolidine-2-carboxylate hydrochloride; 1H NMR (400 MHz, CDCl3) δ ppm 1.32 (t, J=7.2 Hz, 3H) 2.00-2.22 (m, 3H) 2.39-2.48 (m, 1H) 3.49-3.67 (m, 2H) 4.29 (q, J=7.2 Hz, 3H) 9.09 (br s, 1H) 10.98 (br s, 1H). The reaction mixture was concentrated

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

Procedure: 1.8 g (0.01 mol) of proline ethyl ester hydrochloride and 1.0 g of triethylamine were added dropwise to 30 ml of benzene and 2.6 g (0.01 mol) of 4-chloro-3-isopropoxycarbonylphenyl isothiocyanate were added thereto. The mixture was stirred at room temperature for an hour, washed with water, dried over anhydrous sodium sulfate, and then concentrated. The residue was purified by means of silica gel column chromatography to give 2.5 g (yield 63%) of the desired product as a yellow glassy substance. were added washed with water dried over anhydrous sodium sulfate concentrated The residue was purified by means of silica gel column chromatography

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

Procedure: 1.8 g (0.01 mol) of proline ethyl ester hydrochloride and 1.0 g of triethylamine were added dropwise to 30 ml of benzene and 2.6 g (0.01 mol) of 4-chloro-3-isopropoxycarbonylphenyl isothiocyanate were added thereto. The mixture was stirred at room temperature for an hour, washed with water, dried over anhydrous sodium sulfate, and then concentrated. The residue was purified by means of silica gel column chromatography to give 2.5 g (yield 63%) of the desired product as a yellow glassy substance. were added washed with water dried over anhydrous sodium sulfate concentrated The residue was purified by means of silica gel column chromatography

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

Procedure: A mixture of (S)-1-tert-butyl 2-ethyl pyrrolidine-1,2-dicarboxylate (200 mg, 0.822 mmol) and HCl in 1,4-dioxane (4110 μl, 16.44 mmol) was allowed to stir for 1 hour. The reaction mixture was concentrated to give (S)-ethyl pyrrolidine-2-carboxylate hydrochloride; 1H NMR (400 MHz, CDCl3) δ ppm 1.32 (t, J=7.2 Hz, 3H) 2.00-2.22 (m, 3H) 2.39-2.48 (m, 1H) 3.49-3.67 (m, 2H) 4.29 (q, J=7.2 Hz, 3H) 9.09 (br s, 1H) 10.98 (br s, 1H). The reaction mixture was concentrated

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

Procedure: A mixture of (S)-1-tert-butyl 2-ethyl pyrrolidine-1,2-dicarboxylate (200 mg, 0.822 mmol) and HCl in 1,4-dioxane (4110 μl, 16.44 mmol) was allowed to stir for 1 hour. The reaction mixture was concentrated to give (S)-ethyl pyrrolidine-2-carboxylate hydrochloride; 1H NMR (400 MHz, CDCl3) δ ppm 1.32 (t, J=7.2 Hz, 3H) 2.00-2.22 (m, 3H) 2.39-2.48 (m, 1H) 3.49-3.67 (m, 2H) 4.29 (q, J=7.2 Hz, 3H) 9.09 (br s, 1H) 10.98 (br s, 1H). The reaction mixture was concentrated

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

Procedure: To dichloromethane solution (350 ml) of 2-ethyl butanoic acid 5.68 g (48.9 mmol) under cooling on ice-water, HOBt 6.76 g (50 mmol), EDC 9.6 g (50 mmol) were added, stirring was continued for 30 min. 2(S)-pyrrolidine-carboxylic acid ethylester hydrochloride 8 g (45 mmol), NMM 4.55 g (45 mmol) were added to the reaction mixture and then stirred at room temperature for overnight. After then, the reaction mixture was washed with water, 1% sodium hydroxide solution, and then water sequentially. The organic layer was dried over sodium sulfate and the solvents were removed in vacuo. Purification by silica gel chromatography gave a desired product as an oil (8.16 g). NMR was consistent with the desired title product. were added stirred at room temperature for overnight After then, the reaction mixture was washed with water, 1% sodium hydroxide solution The organic layer was dried over sodium sulfate the solvents were removed in vacuo Purification by silica gel chromatography

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

Procedure: 1.8 g (0.01 mol) of proline ethyl ester hydrochloride and 1.0 g of triethylamine were added dropwise to 30 ml of benzene and 2.6 g (0.01 mol) of 4-chloro-3-isopropoxycarbonylphenyl isothiocyanate were added thereto. The mixture was stirred at room temperature for an hour, washed with water, dried over anhydrous sodium sulfate, and then concentrated. The residue was purified by means of silica gel column chromatography to give 2.5 g (yield 63%) of the desired product as a yellow glassy substance. were added washed with water dried over anhydrous sodium sulfate concentrated The residue was purified by means of silica gel column chromatography

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

Procedure: A mixture of (S)-1-tert-butyl 2-ethyl pyrrolidine-1,2-dicarboxylate (200 mg, 0.822 mmol) and HCl in 1,4-dioxane (4110 μl, 16.44 mmol) was allowed to stir for 1 hour. The reaction mixture was concentrated to give (S)-ethyl pyrrolidine-2-carboxylate hydrochloride; 1H NMR (400 MHz, CDCl3) δ ppm 1.32 (t, J=7.2 Hz, 3H) 2.00-2.22 (m, 3H) 2.39-2.48 (m, 1H) 3.49-3.67 (m, 2H) 4.29 (q, J=7.2 Hz, 3H) 9.09 (br s, 1H) 10.98 (br s, 1H). The reaction mixture was concentrated