tert-butyl (2S)-2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate

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

Procedure: Following a procedure analogous to Example 27, from the carboxylic acid (6b, 390 mg, 1.41 mmol) of Example 9 or 16 and (S)-tert-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (573 mg) described in Reference Example 6, 555 mg of the title compound was afforded (yield 80.1%).

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a n-butanol (10 ml) solution of 2-(3,4-dimethoxyphenoxy)acetonitrile (1.26 g) and (S)-t-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (500 mg), K2CO3 (150 mg) was added. The resulting mixture was stirred at 160° C. for an hour under microwave irradiation. After distilling off the solvent under reduced pressure, water was added, followed by extraction with ethyl acetate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel chromatography and NH-form silica gel chromatography to give the titled compound (281 mg). After distilling off the solvent under reduced pressure, water was added followed by extraction with ethyl acetate After distilling off the solvent under reduced pressure the residue was purified by silica gel chromatography and NH-form silica gel chromatography

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a n-butanol (10 ml) solution of 2-(3,4-dimethoxyphenoxy)acetonitrile (1.26 g) and (S)-t-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (500 mg), K2CO3 (150 mg) was added. The resulting mixture was stirred at 160° C. for an hour under microwave irradiation. After distilling off the solvent under reduced pressure, water was added, followed by extraction with ethyl acetate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel chromatography and NH-form silica gel chromatography to give the titled compound (281 mg). After distilling off the solvent under reduced pressure, water was added followed by extraction with ethyl acetate After distilling off the solvent under reduced pressure the residue was purified by silica gel chromatography and NH-form silica gel chromatography

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

Procedure: A mixture of CHCl3 (100 mL) with (S)-t-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (4.791 g), 2-((t-butyldiphenylsilyl)oxy)acetic acid (6.28 g), WSC.HCl (4.371 g) and HOBt.H2O (3.081 g) was stirred at room temperature for 15 hours. To the reaction mixture, a saturated aqueous solution of NH4Cl (500 mL) was added, followed by extraction with AcOEt (500 mL). The organic layer was washed successively with saturated aqueous sodium bicarbonate (500 mL) and brine (500 mL), dried (MgSO4), filtered and concentrated to give a crude product, which was further purified by silica gel chromatography (AcOEt/hexane) to give the titled compound (6.42 g, colorless amorphous.) followed by extraction with AcOEt (500 mL) The organic layer was washed successively with saturated aqueous sodium bicarbonate (500 mL) and brine (500 mL) dried (MgSO4) filtered concentrated to give a crude product, which was further purified by silica gel chromatography (AcOEt/hexane)

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

Procedure: To a solution of (S)-t-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (50.0 g) and 2-(3,4-dimethoxyphenoxy)acetic acid (47.8 g) in chloroform (1000 ml), HOBt (35.3 g) and WSC hydrochloride (50.0 g) were added and the mixture was stirred at room temperature for 4 hours. After distilling off the solvent under reduced pressure, water was added, followed by extraction with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium bicarbonate and brine and dried over MgSO4 before it was filtered. The solvent was distilled off under reduced pressure to give a crude form of the titled compound (61.0 g). After distilling off the solvent under reduced pressure, water was added followed by extraction with ethyl acetate The organic layer was washed successively with saturated aqueous sodium bicarbonate and brine dried over MgSO4 before it was filtered The solvent was distilled off under reduced pressure

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

Procedure: To a solution of (S)-t-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (50.0 g) and 2-(3,4-dimethoxyphenoxy)acetic acid (47.8 g) in chloroform (1000 ml), HOBt (35.3 g) and WSC hydrochloride (50.0 g) were added and the mixture was stirred at room temperature for 4 hours. After distilling off the solvent under reduced pressure, water was added, followed by extraction with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium bicarbonate and brine and dried over MgSO4 before it was filtered. The solvent was distilled off under reduced pressure to give a crude form of the titled compound (61.0 g). After distilling off the solvent under reduced pressure, water was added followed by extraction with ethyl acetate The organic layer was washed successively with saturated aqueous sodium bicarbonate and brine dried over MgSO4 before it was filtered The solvent was distilled off under reduced pressure

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

Procedure: Following a procedure analogous to Example 27, from the carboxylic acid (6b, 390 mg, 1.41 mmol) of Example 9 or 16 and (S)-tert-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (573 mg) described in Reference Example 6, 555 mg of the title compound was afforded (yield 80.1%).

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a n-butanol (10 ml) solution of 2-(3,4-dimethoxyphenoxy)acetonitrile (1.26 g) and (S)-t-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (500 mg), K2CO3 (150 mg) was added. The resulting mixture was stirred at 160° C. for an hour under microwave irradiation. After distilling off the solvent under reduced pressure, water was added, followed by extraction with ethyl acetate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel chromatography and NH-form silica gel chromatography to give the titled compound (281 mg). After distilling off the solvent under reduced pressure, water was added followed by extraction with ethyl acetate After distilling off the solvent under reduced pressure the residue was purified by silica gel chromatography and NH-form silica gel chromatography

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

Procedure: A mixture of CHCl3 (100 mL) with (S)-t-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (4.791 g), 2-((t-butyldiphenylsilyl)oxy)acetic acid (6.28 g), WSC.HCl (4.371 g) and HOBt.H2O (3.081 g) was stirred at room temperature for 15 hours. To the reaction mixture, a saturated aqueous solution of NH4Cl (500 mL) was added, followed by extraction with AcOEt (500 mL). The organic layer was washed successively with saturated aqueous sodium bicarbonate (500 mL) and brine (500 mL), dried (MgSO4), filtered and concentrated to give a crude product, which was further purified by silica gel chromatography (AcOEt/hexane) to give the titled compound (6.42 g, colorless amorphous.) followed by extraction with AcOEt (500 mL) The organic layer was washed successively with saturated aqueous sodium bicarbonate (500 mL) and brine (500 mL) dried (MgSO4) filtered concentrated to give a crude product, which was further purified by silica gel chromatography (AcOEt/hexane)

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

Procedure: To a solution of (S)-t-butyl 2-(hydrazinecarbonyl)pyrrolidine-1-carboxylate (50.0 g) and 2-(3,4-dimethoxyphenoxy)acetic acid (47.8 g) in chloroform (1000 ml), HOBt (35.3 g) and WSC hydrochloride (50.0 g) were added and the mixture was stirred at room temperature for 4 hours. After distilling off the solvent under reduced pressure, water was added, followed by extraction with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium bicarbonate and brine and dried over MgSO4 before it was filtered. The solvent was distilled off under reduced pressure to give a crude form of the titled compound (61.0 g). After distilling off the solvent under reduced pressure, water was added followed by extraction with ethyl acetate The organic layer was washed successively with saturated aqueous sodium bicarbonate and brine dried over MgSO4 before it was filtered The solvent was distilled off under reduced pressure