1-Boc-2-Cbz-hydrazine

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2-chloromethyl-propene ( 5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature unit the reaction is complete by TLC. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature unit the reaction The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated

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

Procedure: 1.5 g (37.5 mmol) of 60% sodium hydride in oil was suspended in 50 mL of DMF to which was added 5.0 g (18.7 mmol) of 1-Boc-2-Cbz-hydrazine dissolved in 20 mL of dry DMF slowly over 30 minutes. The reaction mixture was stirred for 1 hour until H2 evolution had ceased. To this mixture was added 2.24 mL (18.77 mmol) of 1,4-dibromobutane neat. The reaction mixture was stirred at room temperature over 3 days. The mixture was concentrated in vacuo and the residue was suspended in 150 mL of EtOAc. The mixture was washed with water twice, 5% citric acid twice, saturated aqueous NaHCO3 solution , water and brine. The solution was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexanes to give the desired product as a white solid. 1H-NMR (CDCl3, 400 MHz):1.45 (bs, 9H); 1.62 (bm, 4H); 2.90 (bs, 2H); 4.15 (bm, 2H); 5.00-5.30 (m, 2H); 7.20-7.40 (bm, 5H). The reaction mixture was stirred at room temperature over 3 days The mixture was concentrated in vacuo The mixture was washed with water twice The solution was dried over MgSO4 filtered concentrated in vacuo The residue was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexanes

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

Procedure: 1.5 g (37.5 mmol) of 60% sodium hydride in oil was suspended in 50 mL of DMF to which was added 5.0 g (18.7 mmol) of 1-Boc-2-Cbz-hydrazine dissolved in 20 mL of dry DMF slowly over 30 minutes. The reaction mixture was stirred for 1 hour until H2 evolution had ceased. To this mixture was added 2.24 mL (18.77 mmol) of 1,4-dibromobutane neat. The reaction mixture was stirred at room temperature over 3 days. The mixture was concentrated in vacuo and the residue was suspended in 150 mL of EtOAc. The mixture was washed with water twice, 5% citric acid twice, saturated aqueous NaHCO3 solution , water and brine. The solution was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexanes to give the desired product as a white solid. 1H-NMR (CDCl3, 400 MHz):1.45 (bs, 9H); 1.62 (bm, 4H); 2.90 (bs, 2H); 4.15 (bm, 2H); 5.00-5.30 (m, 2H); 7.20-7.40 (bm, 5H). The reaction mixture was stirred at room temperature over 3 days The mixture was concentrated in vacuo The mixture was washed with water twice The solution was dried over MgSO4 filtered concentrated in vacuo The residue was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexanes

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2-chloromethyl-propene (5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature until the reaction is complete by TLC, approximately 12 hours. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature until the reaction is complete by TLC, approximately 12 hours The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2-chloromethyl-propene ( 5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature unit the reaction is complete by TLC. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature unit the reaction The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2-chloromethyl-propene ( 5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature unit the reaction is complete by TLC. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature unit the reaction The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2chloromethyl-propene (5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature until the reaction is complete by TLC, approximately 12 hours. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature until the reaction is complete by TLC, approximately 12 hours The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2-chloromethyl-propene (5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature until the reaction is complete by TLC, approximately 12 hours. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature until the reaction is complete by TLC, approximately 12 hours The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2chloromethyl-propene (5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature until the reaction is complete by TLC, approximately 12 hours. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature until the reaction is complete by TLC, approximately 12 hours The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2-chloromethyl-propene (5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature until the reaction is complete by TLC, approximately 12 hours. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature until the reaction is complete by TLC, approximately 12 hours The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2-chloromethyl-propene (5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature until the reaction is complete by TLC, approximately 12 hours. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature until the reaction is complete by TLC, approximately 12 hours The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated

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

Procedure: To a suspension of NaH (3.81 g, 95.4 mmol) in DMF (80 mL) is add dropwise a solution of N-Cbz-N′-Boc-hydrazine (12.1 g, 45.4 mmol) in DMF (20 mL). The reaction mixture is stirred about 20 minutes and 3-chloro-2-chloromethyl-propene (5.8 mL, 50 mmol) is added dropwise and the reaction is allowed to stir at room temperature until the reaction is complete by TLC, approximately 12 hours. The reaction solution is partitioned between ethyl acetate and water, the water layer being extracted several times more with solvent. The combined organic layers are dried, filtered, and concentrated to afford the desired product as a clear oil which is used without further purification. to stir at room temperature until the reaction is complete by TLC, approximately 12 hours The reaction solution is partitioned between ethyl acetate and water the water layer being extracted several times more with solvent The combined organic layers are dried filtered concentrated