9H-fluoren-9-ylmethyl N-aminocarbamate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Using anhydrous conditions and under a nitrogen gas blanket, a 200 ml round bottom flask was charged with 4.90 g (10.48 mmol) of N-BOC-6-aminocaproate (N-(FMOC) hydrazide), and 10 ml of methylene chloride. The reaction mixture was then stirred at room temperature as 16 ml of trifluoroacetic acid (Schweizerhall) dissolved in 16 ml of methylene chloride was slowly added. The resultant homogeneous solution was allowed to stir for an additional 2 h and then 15 ml of toluene was added. The solvents and any remaining trifluoroacetic acid were then distilled off under reduced pressure. The distillation residue was twice more azeotroped with 15 ml portions of toluene to leave 8.49 g of orange oil. 1H NMR showed this crude material to contain the peaks associated with aminocaproic acid and a FMOC substituent. However, no tert-butyl peak was observed between 1-2 ppm showing removal of the BOC protecting group. This product was used without further purification. removal of the BOC protecting group This product was used without further purification

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

Procedure: Using anhydrous conditions and under a nitrogen gas blanket, a 200 ml round bottom flask was charged with 4.90 g (10.48 mmol) of N-BOC-6-aminocaproate (N-(FMOC) hydrazide), and 10 ml of methylene chloride. The reaction mixture was then stirred at room temperature as 16 ml of trifluoroacetic acid (Schweizerhall) dissolved in 16 ml of methylene chloride was slowly added. The resultant homogeneous solution was allowed to stir for an additional 2 h and then 15 ml of toluene was added. The solvents and any remaining trifluoroacetic acid were then distilled off under reduced pressure. The distillation residue was twice more azeotroped with 15 ml portions of toluene to leave 8.49 g of orange oil. 1H NMR showed this crude material to contain the peaks associated with aminocaproic acid and a FMOC substituent. However, no tert-butyl peak was observed between 1-2 ppm showing removal of the BOC protecting group. This product was used without further purification. removal of the BOC protecting group This product was used without further purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 ml round bottom flask was charged with 4.190 g (0.0181 mol) of N-BOC-6-aminocaproic acid, 4.60 g of 9-fluorenylmethyl carbazate (FMOC), (prepared by the method of Carpino et. al., 1972, J. Org. Chem., 37: 3404) and 35 ml of N,N-dimethylformamide. The reaction solution was cooled to 0° C. and then 3.75 g (0.0182 mol) of 1,3-dicyclohexylcarbodiimide (Aldrich) was added. The reaction mixture was allowed to stir for 2 h at 0° C. The white precipitate which formed during this time was filtered off and the solvents evaporated under reduced pressure. The distillation residue was applied to a 225 cc pad of silica gel (Merck), which was then washed with 1L of chloroform. The product was then eluted from the column using 1 L of 50% methanol in chloroform. The solvents were evaporated from the desired eluent fractions to give 4.98 g (0.011 mol, 59% yield) of N-BOC-6-aminocaproic acid (N'-FMOC-hydrazide) as a yellow oil. 1H NMR (DMSO-d6) showed the peaks observed in the starting material and new protons in the aromatic region between 7-8 ppm (FMOC group). (prepared by the method of Carpino et. al., 1972, J The white precipitate which formed during this time was filtered off the solvents evaporated under reduced pressure was then washed with 1L of chloroform The product was then eluted from the column The solvents were evaporated from the desired eluent fractions

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 ml round bottom flask was charged with 4.190 g (0.0181 mol) of N-BOC-6-aminocaproic acid, 4.60 g of 9-fluorenylmethyl carbazate (FMOC), (prepared by the method of Carpino et. al., 1972, J. Org. Chem., 37: 3404) and 35 ml of N,N-dimethylformamide. The reaction solution was cooled to 0° C. and then 3.75 g (0.0182 mol) of 1,3-dicyclohexylcarbodiimide (Aldrich) was added. The reaction mixture was allowed to stir for 2 h at 0° C. The white precipitate which formed during this time was filtered off and the solvents evaporated under reduced pressure. The distillation residue was applied to a 225 cc pad of silica gel (Merck), which was then washed with 1L of chloroform. The product was then eluted from the column using 1 L of 50% methanol in chloroform. The solvents were evaporated from the desired eluent fractions to give 4.98 g (0.011 mol, 59% yield) of N-BOC-6-aminocaproic acid (N'-FMOC-hydrazide) as a yellow oil. 1H NMR (DMSO-d6) showed the peaks observed in the starting material and new protons in the aromatic region between 7-8 ppm (FMOC group). (prepared by the method of Carpino et. al., 1972, J The white precipitate which formed during this time was filtered off the solvents evaporated under reduced pressure was then washed with 1L of chloroform The product was then eluted from the column The solvents were evaporated from the desired eluent fractions

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

Procedure: Using anhydrous conditions and under a nitrogen gas blanket, a 200 ml round bottom flask was charged with 4.90 g (10.48 mmol) of N-BOC-6-aminocaproic acid, N'-FMOC hydrazide, 8, and 10 ml of methylene chloride. The reaction mixture was then stirred at room temperature as 16 ml of trifluoroacetic acid (Schweizerhall) dissolved in 16 ml of methylene chloride was slowly added. The resultant homogeneous solution was allowed to stir for an additional 2 h and then 15 ml of toluene was added. The solvents and any remaining trifluoroacetic acid were then distilled off under reduced pressure. The distillation residue was twice more azeotroped with 15 ml portions of toluene to leave 8.49 g of orange oil. 1H NMR showed this crude material to contain the peaks associated with aminocaproic acid and a FMOC substituent. However, no tert-butyl peak was observed between 1-2 ppm showing removal of the BOC protecting group. This product was used without further purification. removal of the BOC protecting group This product was used without further purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 ml round bottom flask was charged with 4.190 g (0.0181 mol) of N-BOC-6-aminocaproic acid, 7, 4.60 g of 9-fluorenylmethyl carbazate (FMOC), (prepared by the method of Carpino et. al., 1972, J. Org. Chem., 37:3404) and 35 ml of N,N-dimethylformamide. The reaction solution was cooled to 0° C. and then 3.75 g (0.0182 mol) of 1,3-dicyclohexylcarbodiimide (Aldrich) was added. The reaction mixture was allowed to stir for 2 h at 0° C. The white precipitate which formed during this time was filtered off and the solvents evaporated under reduced pressure. The distillation residue was applied to a 225 cc pad of silica gel (Merck), which was then washed with 1L of chloroform. The product was then eluted from the column using 1L of 50% methanol in chloroform. The solvents were evaporated from the desired eluent fractions to give 4.98 g (0.011 mol, 59% yield) of N-BOC-6-aminocaproic acid, N'-FMOC hydrazide, 8, as a yellow oil. 1H NMR (DMSO-d6, TMS) showed the peaks observed in the starting material and new protons in the aromatic region between 7-8 ppm (FMOC group). (prepared by the method of Carpino et. al., 1972, J The white precipitate which formed during this time was filtered off the solvents evaporated under reduced pressure was then washed with 1L of chloroform The product was then eluted from the column The solvents were evaporated from the desired eluent fractions

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 250 ml round bottom flask was charged with 4.190 g (0.0181 mol) of N-BOC-6-aminocaproic acid, 7, 4.60 g of 9-fluorenylmethyl carbazate (FMOC), (prepared by the method of Carpino et. al., 1972, J. Org. Chem., 37:3404) and 35 ml of N,N-dimethylformamide. The reaction solution was cooled to 0° C. and then 3.75 g (0.0182 mol) of 1,3-dicyclohexylcarbodiimide (Aldrich) was added. The reaction mixture was allowed to stir for 2 h at 0° C. The white precipitate which formed during this time was filtered off and the solvents evaporated under reduced pressure. The distillation residue was applied to a 225 cc pad of silica gel (Merck), which was then washed with 1L of chloroform. The product was then eluted from the column using 1L of 50% methanol in chloroform. The solvents were evaporated from the desired eluent fractions to give 4.98 g (0.011 mol, 59% yield) of N-BOC-6-aminocaproic acid, N'-FMOC hydrazide, 8, as a yellow oil. 1H NMR (DMSO-d6, TMS) showed the peaks observed in the starting material and new protons in the aromatic region between 7-8 ppm (FMOC group). (prepared by the method of Carpino et. al., 1972, J The white precipitate which formed during this time was filtered off the solvents evaporated under reduced pressure was then washed with 1L of chloroform The product was then eluted from the column The solvents were evaporated from the desired eluent fractions

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

Procedure: To a well-stirred solution of hydrazine hydrate (19 g, 386 mmol) in 150 mL of CH3CN/H2O (1/1, v/v), a solution of FmocCl (10 g, 38.65 mmol) in 600 mL CH3CN was added dropwise at 0° C. over 2 h. The reaction mixture was then allowed to warm to room temperature and stirred for an additional 12 hours, concentrated in vacuo to 150 mL and filtered to yield the title compound as a white solid, which was washed with water and hexane and dried to a constant weight in vacuo (9.74 g, 99%): mp 172-173° C.; 1H NMR (DMSO) □ 4.08 (brs, 2H), 4.21 (t, J=7.2 Hz, 1H), 4.28 (d, J=7.2 Hz, 2H), 7.32 (t, J=7.4 Hz, 2H), 7.42 (t, J=7.4 Hz, 2H), 7.69 (d, J=7.4 Hz, 2H), 7.89 (d, J=7.4 Hz, 2H), 8.36 (brs, 1H); 13C NMR (DMSO) □□ 47.7, 66.7, 121.1 (2C), 126.3 (2C), 128.1 (2C), 128.7 (2C), 141.7 (2C), 144.9 (2C), 159.2. concentrated in vacuo to 150 mL filtered

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

Procedure: 2.0 mmol of 3-phenylglutaric anhydride and 2.0 mmol of Fmoc-hydrazine are dissolved in 30 ml of THF and heated under reflux for 16 hours. The product is then extracted with 50 ml of DCM and 50 ml of 1N HCl solution and the organic phase is dried with MgSO4 and filtered off. Removal of the solvent gives 5-[N′-(9H-fluoren-9-ylmethoxycarbonyl)hydrazino]-5-oxo-3-phenylpentanoic acid. heated under reflux for 16 hours The product is then extracted with 50 ml of DCM and 50 ml of 1N HCl solution the organic phase is dried with MgSO4 filtered off Removal of the solvent

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

Procedure: 2.0 mmol of 3-phenylglutaric anhydride and 2.0 mmol of Fmoc-hydrazine are dissolved in 30 ml of THF and heated under reflux for 16 hours. The product is then extracted with 50 ml of DCM and 50 ml of 1N HCl solution and the organic phase is dried with MgSO4 and filtered off. Removal of the solvent gives 5-[N′-(9H-fluoren-9-ylmethoxycarbonyl)hydrazino]-5-oxo-3-phenylpentanoic acid. heated under reflux for 16 hours The product is then extracted with 50 ml of DCM and 50 ml of 1N HCl solution the organic phase is dried with MgSO4 filtered off Removal of the solvent

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

Procedure: 2 equivalents of phosgene (1.89M in toluene; 4.2 ml) are added to a solution of 3.91 mmol of 9H-fluoren-9-ylmethyl hydrazinecarboxylate in 40 ml of dichloromethane and 40 ml of saturated aqueous NaHCO3 solution. The mixture is stirred for 15 minutes and then worked up as usual, giving 5-(9H-fluoren-9-ylmethoxy)-3H-[1,3,4]oxadiazol-2-one (“AB”)