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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-[[[(4-Methylphenyl)sulfonyl]oxy]methyl]-1-pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester (3.55 g, 10 mmol, see J. Das et al, J. Med Chem, 1992, Vol.35,2610 for preparation) was dissolved in dimethyl sulfoxide (DMSO) (40 mL) and treated with sodium azide (980 mg, 15 mmol). The mixture was heated at 70° C. for 5 hours, then cooled and diluted with ether. After washing with water (3×50 mL), the ether layer was dried (MgSO4) and freed of solvent in vacuo to give title compound as a colorless oil (2.05 g, 91%) which was used without further purification. cooled After washing with water (3×50 mL) the ether layer was dried (MgSO4)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sealed tube was charged with p-toluenesulfonyl cyanide (5.0 g, 22.1 mmol) and (S)-Boc-2-azido methyl pyrrolidine (1) [Black, J.; Brown, A. D.; Erizabet C. L.; Smith, J. D,; Mckelloy, A. B. 2000 JP2000063380/] (4.0 g, 22.1 mmol). The mixture was stirred at 80° C. for 40 hrs. The crude product was purified on flash silica gel column with (Hexane:EtOAc=1:1) to furnish 2 (7.6 g, 84%) as colorless foam. [α]D −11.7 (c 0.64, CHCl3). 1H NMR (400 MHz, CD3OD, −20° C., rotamers 6:4): δ 1.20 & 1.35 (s, 9H), 1.83 & 2.01 (m, 4H), 2.50 (s, 3H) 3.40 & 3.45 (m, 2H), 4.40 & 4.43 (m, 1H), 4.71 & 4.82 (m, 2H), 7.50 & 7.70 (d, J=8 Hz, 2H), 8.00 & 8.40 (d, J=8 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 22.0, 23.7, 28.4, 46.5, 52.1, 56.1, 76.9, 80.6, 129.4, 134.4, 147.4, 154.4, 154.8, 155.5; IR (film): 2976, 1693, 1392, 815, 704 cm−1; MS: (ESI) [M+1]+ 408.2. The crude product was purified on flash silica gel column with (Hexane:EtOAc=1:1)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-[[[(4-Methylphenyl)sulfonyl]oxy]methyl]-1-pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester (3.55 g, 10 mmol, see J. Das et al, J. Med Chem, 1992, Vol.35, 2610 for preparation) was dissolved in dimethyl sulfoxide (DMSO) (40 mL) and treated with sodium azide (980 mg, 15 mmol). The mixture was heated at 70° C. for 5 hours, then cooled and diluted with ether. After washing with water (3×50 mL), the ether layer was dried (MgSO4) and freed of solvent in vacuo to give title compound as a colorless oil (2.05 g, 91%) which was used without further purification. cooled After washing with water (3×50 mL) the ether layer was dried (MgSO4)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-[[[(4-Methylphenyl)sulfonyl]oxy]methyl]-1-pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester (3.55 g, 10 mmol, see J. Das et al, J. Med Chem, 1992, Vol. 35,2610 for preparation) was dissolved in dimethyl sulfoxide (DMSO) (40 mL) and treated with sodium azide (980 mg, 15 mmol). The mixture was heated at 70° C. for 5 hours, then cooled and diluted with ether. After washing with water (3×50 mL), the ether layer was dried (MgSO4) and freed of solvent in vacuo to give title compound as a colorless oil (2.05 g, 91%) which was used without further purification. cooled After washing with water (3×50 mL) the ether layer was dried (MgSO4)

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

Procedure: (S)-2-(azidomethyl)-1-Boc-pyrrolidine (480 mg, 2.1 mmol) was added to a flask containing p-toluenesulfonyl cyanide (420 mg, 2.3 mmol) and a stir bar (no solvent). The flask was placed in a 80° C. bath and reaction proceeded for 48 hours. The reaction was concentrated in vacuo. The crude amber oil was purified by flash silica gel chromatography using a hexane/ethyl acetate gradient. The product (780 mg, 91% yield) was obtained as a colorless oil. 1H-NMR (500 MHz, CDCl3): δ 8.01 (broad d, J=18 Hz, 2H), 7.44 (m, 3H), 4.85-4.70 (m, 2H), 4.52-4.48 (m, 1H), 3.50-3.34 (m, 2H), 2.49 (s, 3H), 2.01-1.71 (m, 4H), 1.40 & 1.33 (2 s, 9H). ESI-MS (m/z) for C18H25N5O4S (exact mass 407.16): [M+H]+ calc. 408.2, obs. 408.2; [M+Na]+ calc. 430.2, obs. 430.2. was placed in a 80° C. reaction The reaction was concentrated in vacuo The crude amber oil was purified by flash silica gel chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A sealed tube was charged with p-toluenesulfonyl cyanide (5.0 g, 22.1 mmol) and (S)-Boc-2-azido methyl pyrrolidine (1) [Black, J.; Brown, A. D.; Erizabet C. L.; Smith, J. D,; Mckelloy, A. B. 2000 JP2000063380/] (4.0 g, 22.1 mmol). The mixture was stirred at 80° C. for 40 hrs. The crude product was purified on flash silica gel column with (Hexane:EtOAc=1:1) to furnish 2 (7.6 g, 84%) as colorless foam. [α]D−11.7 (c 0.64, CHCl3). 1H NMR (400 MHz, CD3OD, −20° C., rotamers 6:4): δ 1.20 & 1.35 (s, 9H), 1.83 & 2.01 (m, 4H), 2.50 (s, 3H) 3.40 & 3.45 (m, 2H), 4.40 & 4.43 (m, 1H), 4.71 & 4.82 (m, 2H), 7.50 & 7.70 (d, J=8 Hz, 2H), 8.00 & 8.40 (d, J=8 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 22.0, 23.7, 28.4, 46.5, 52.1, 56.1, 76.9, 80.6, 129.4, 134.4, 147.4, 154.4, 154.8, 155.5; IR (film): 2976, 1693, 1392, 815, 704 cm−1; MS: (ESI) [M+1]+ 408.2. The crude product was purified on flash silica gel column with (Hexane:EtOAc=1:1)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-2-[[[(4-Methylphenyl)sulfonyl]oxy]methyl]-1-pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester (3.55 g, 10 mmol, see J. Das et al, J. Med Chem, 1992, Vol.35,2610 for preparation) was dissolved in dimethyl sulfoxide (DMSO) (40 mL) and treated with sodium azide (980 mg, 15 mmol). The mixture was heated at 70° C. for 5 hours, then cooled and diluted with ether. After washing with water (3×50 mL), the ether layer was dried (MgSO4) and freed of solvent in vacuo to give title compound as a colorless oil (2.05 g, 91%) which was used without further purification. cooled After washing with water (3×50 mL) the ether layer was dried (MgSO4)