tetrabutylazanium;azide

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

Procedure: 5-(R)-Chloromethyloxazolidine-2-one (prepared according to [Danielmeier et al. Efficient Pathways to (R)- and (S)-hydroxymethyl-2-oxazolidinone and some derivatives. Tetrahedron: Asymmetry. 1995, vol. 6, pp. 1181-1190] (5 mmol) is reacted with sodium azide (7-10 mmol) in acetone (ca. 40-50 mL) at r.t. for ca. 24 h (until the reaction is completed). Solids are filtered off, and supernatant evaporated under vacuum to afford the product which is immediately used for the next step. Optionally, the synthesis is performed in dry N,N-dimethylformamide under inert atmosphere with sodium azide (5-10 mmol) or tetrabutylammonium azide (5-10 mmol), and the resulting solution of the crude 5-(S)-azidomethyloxazolidine-2-one is employed for the next step without solvent removal. Solids are filtered off supernatant evaporated under vacuum to afford the product which the resulting solution of the crude 5-(S)-azidomethyloxazolidine-2-one is employed for the next step without solvent removal

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.70 g of toluene-4-sulfonic acid 1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4-yl-methyl ester (1.57 mmol), 0.308 g of sodium azide (4.70 mmol) and 0.20 g of tetrabutylammonium azide (0.70 mmol) are mixed in 3.50 ml of dimethyl sulfoxide. The mixture is heated at 110° C. under a nitrogen atmosphere for 20 hours. The reaction mixture is poured into ice-cold water and then extracted with ethyl acetate. The organic phase is washed with water and then with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered and concentrated under vacuum. The title product is isolated by chromatography on a neutral alumina column (eluent: hexane/ethyl acetate; 70:30). 0.313 g of a yellow oil is obtained. The reaction mixture is poured into ice-cold water extracted with ethyl acetate The organic phase is washed with water with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate filtered concentrated under vacuum

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

Procedure: 13.6 g of freshly dried tetrabutylammonium azide are added to a solution, stirred at room temperature, of 17.8 g of 3(S)-isopropyl-5(S)-{1(R)-bromo-4-methyl-3(S)-[(4(S)-benzyloxazolidin-2-on-3-yl)-carbonyl]-pentyl}-tetrahydrofuran-2-one in 180 ml of toluene, and a further 10 g of the azide are added in the course of 160 hours' stirring at room temperature. The reaction mixture is then partitioned between ethyl acetate and water (2x) and saturated sodium chloride solution (1x). The organic phases are combined, dried over sodium sulfate and concentrated. The title compound is obtained from the evaporation residue by means of FC (hexane/ethyl acetate=8:2) and crystallisation from diethyl ether/hexane: m.p.=102°-103° C.; Rf (hexane/ethyl acetate=8:2)=0.2; HPLC Rt =18.55 minutes; FAB-MS (M+H)+=457. The reaction mixture is then partitioned between ethyl acetate and water (2x) and saturated sodium chloride solution (1x) dried over sodium sulfate concentrated

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

Procedure: 13.6 g of freshly dried tetrabutylammonium azide are added to a solution, stirred at room temperature, of 17.8 g of 3(S)-isopropyl-5(S)-{1(R)-bromo-4-methyl-3(S)-[(4(S)-benzyloxazolidin-2-on-3-yl)-carbonyl]-pentyl}-tetrahydrofuran-2-one in 180 ml of toluene, and a further 10 g of the azide are added in the course of 160 hours' stirring at room temperature. The reaction mixture is then partitioned between ethyl acetate and water (2x) and saturated sodium chloride solution (1x). The organic phases are combined, dried over sodium sulfate and concentrated. The title compound is obtained from the evaporation residue by means of FC (hexane/ethyl acetate=8:2) and crystallisation from diethyl ether/hexane: m.p.=102°-103° C.; Rf (hexane/ethyl acetate=8:2)=0.2; HPLC Rt =18.55 minutes; FAB-MS (M+H)+=457. The reaction mixture is then partitioned between ethyl acetate and water (2x) and saturated sodium chloride solution (1x) dried over sodium sulfate concentrated

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

Procedure: tert-Butyl 3,3-difluoro-4-{[(trifluoromethyl)sulfonyl]oxy}pyrrolidine-1-carboxylate (5.56 g, 15.2 mmol) was dissolved in DMF (20 mL) and cooled in an ice bath under nitrogen atmosphere. Tetrabutylammonium azide (TBA-N3, 4.8 g, 17 mmol, 1.1 mol eq) in DMF (15 mL) was added slowly over 15 min via an addition funnel. The reaction mixture was stirred in the cold bath and was allowed to warm to ambient temperature gradually. After 16 hr, the reaction was diluted with MTBE (300 mL), washed with sat. aq. NaHCO3 (2×30 mL), and brine (2×30 mL), dried over Na2SO4 and evaporated to give a residue. This crude material was purified on silica (40 g) with gradients from 100% heptane to 20% ethyl acetate-80% heptane to give the title product as a colorless oil (3.02 g, 80% yield, >95% purity). 1H NMR (400 MHz, chloroform-d) δ ppm 4.06 (dtd, J=8.86, 5.41, 5.41, 3.91 Hz, 1 H) 3.65-3.83 (m, 3 H) 3.36-3.57 (m, 1 H) 1.47 (s, 9 H). 19F NMR (376 MHz, chloroform-d) δ ppm −106.10-−102.44 (m, 1 F) −120.14-−116.68 (m, 1 F). m/z (ESI+) for C9H14F2N4O2 149 (small)/123 (M+H)+. cooled in an ice bath under nitrogen atmosphere washed with sat. aq. NaHCO3 (2×30 mL), and brine (2×30 mL) dried over Na2SO4 evaporated to give a residue This crude material was purified on silica (40 g) with gradients from 100% heptane to 20% ethyl acetate-80% heptane

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

Procedure: Compound 47 (4.3) (1 mmol) was taken in anhydrous acetone (25 mL) and tetra-n-butylammonium azide (2 mmol) was added and the reaction was refluxed for 8 h. The reaction was cooled to RT and solvent was evaporated on Rotavapor to give a crude compound which on purification by Biotage SP1 provided pure N-(4-azidobutyl)-N-methyl-4-phenyl-1H-imidazole-1-carboxamide (48/4.4). the reaction was refluxed for 8 h solvent was evaporated on Rotavapor to give a crude compound which on purification by Biotage SP1

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

Procedure: 5-(R)-Chloromethyloxazolidine-2-one (prepared according to [Danielmeier et al. Efficient Pathways to (R)- and (S)-hydroxymethyl-2-oxazolidinone and some derivatives. Tetrahedron: Asymmetry. 1995, vol. 6, pp. 1181-1190] (5 mmol) is reacted with sodium azide (7-10 mmol) in acetone (ca. 40-50 mL) at r.t for ca, 24 h (until the reaction is completed). Solids are filtered off, and supernatant evaporated under vacuum to afford the product which is immediately used for the next step. Optionally, the synthesis is performed in dry N,N-dimethylformamide under inert atmosphere with sodium azide (5-10 mmol) or tetrabutylammonium azide (5-10 mmol), and the resulting solution of the crude 5-(S)-azidomethyloxazolidine-2-one is employed for the next step without solvent removal. Solids are filtered off supernatant evaporated under vacuum to afford the product which the resulting solution of the crude 5-(S)-azidomethyloxazolidine-2-one is employed for the next step without solvent removal

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

Procedure: Methyl 3,4,6-tri-O-benzyl-2-O-trifluoromethanesulfonyl-α-L-mannopyranoside (6) (12.23 g) was dissolved in dehydrated benzene (400 ml), tetrabutylammonium azide [(n-Bu)4NN3] (29.16 g) was added thereto under an argon atmosphere. After 3 days, (n-Bu)4NN3 (3.61 g) was further added thereto. The mixture was stirred at room temperature for an additional 11 days (14 days in total). The reaction mixture was charged to a silica gel column as such to effect purification by silica gel column chromatography combined with preparative thin-layer chromatography, whereby a target product was obtained (yield: 3.58 g, yield ratio: 36%). The reaction mixture was charged to a silica gel column as such purification by silica gel column chromatography was obtained (yield: 3.58 g, yield ratio: 36%)

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

Procedure: 13.6 g of freshly dried tetrabutylammonium azide are added to a solution, stirred at room temperature, of 17.8 g of 3(S)-isopropyl-5(S)-{1(R)-bromo-4-methyl-3(S)-[(4(S)-benzyl-oxazolidin-2-on-3-yl)-carbonyl]-pentyl}-tetrahydrofuran-2-one in 180 ml of toluene, and a further 10 g of the azide are added in the course of 160 hours' stirring at room temperature. The reaction mixture is then partitioned between ethyl acetate and water (2x) and saturated sodium chloride solution (1x). The organic phases are combined, dried over sodium sulfate and concentrated. The title compound is obtained from the evaporation residue by means of FC (hexane/ethyl acetate=8:2) and crystallisation from diethyl ether/hexane: m.p.=102°-103° C.; Rf (hexane/ethyl acetate=8:2)=0.2; HPLC Rt =18.55 minutes; FAB-MS (M+H)+ =457. The reaction mixture is then partitioned between ethyl acetate and water (2x) and saturated sodium chloride solution (1x) dried over sodium sulfate concentrated

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

Procedure: 13.6 g of freshly dried tetrabutylammonium azide are added to a solution, stirred at room temperature, of 17.8 g of 3(S)-isopropyl-5(S)-{1(R)-bromo-4-methyl-3(S)-[(4(S)-benzyl-oxazolidin-2-on-3-yl)-carbonyl]-pentyl}-tetrahydrofuran-2-one in 180 ml of toluene, and a further 10 g of the azide are added in the course of 160 hours' stirring at room temperature. The reaction mixture is then partitioned between ethyl acetate and water (2x) and saturated sodium chloride solution (1x). The organic phases are combined, dried over sodium sulfate and concentrated. The title compound is obtained from the evaporation residue by means of FC (hexane/ethyl acetate=8:2) and crystallisation from diethyl ether/hexane: m.p.=102°-103° C.; Rf (hexane/ethyl acetate=8:2)=0.2; HPLC Rt =18.55 minutes; FAB-MS (M+H)+ =457. The reaction mixture is then partitioned between ethyl acetate and water (2x) and saturated sodium chloride solution (1x) dried over sodium sulfate concentrated

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

Procedure: 13.6 g of freshly dried tetrabutylammonium azide are added to a solution, stirred at room temperature, of 17.8 g of 3(S)-isopropyl-5(S)-{1(R)-bromo-4-methyl-3(S)-[(4(S)-benzyloxazolidin-2-on-3-yl)-carbonyl]-pentyl}-tetrahydrofuran-2-one in 180 ml of toluene, and a further 10 g of the azide are added in the course of 160 hours' stirring at room temperature. The reaction mixture is then partitioned between ethyl acetate and water (2×) and saturated sodium chloride solution (1×). The organic phases are combined, dried over sodium sulfate and concentrated. The title compound is obtained from the evaporation residue by means of FC (hexane/ethyl acetate=8:2) and crystallisation from diethyl ether/hexane: m.p.=102°-103° C.; Rf (hexane/ethyl acetate=8:2)=0.2; HPLC Rt =18.55 minutes; FAB-MS (M+H)+ =457. The reaction mixture is then partitioned between ethyl acetate and water (2×) and saturated sodium chloride solution (1×) dried over sodium sulfate concentrated

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

Procedure: 13.6 g of freshly dried tetrabutylammonium azide are added to a solution, stirred at room temperature, of 17.8 g of 3(S)-isopropyl-5(S)-{1(R)-bromo-4-methyl-3(S)-[(4(S)-benzyloxazolidin-2-on-3-yl)-carbonyl]-pentyl}-tetrahydrofuran-2-one in 180 ml of toluene, and a further 10 g of the azide are added in the course of 160 hours' stirring at room temperature. The reaction mixture is then partitioned between ethyl acetate and water (2×) and saturated sodium chloride solution (1×). The organic phases are combined, dried over sodium sulfate and concentrated. The title compound is obtained from the evaporation residue by means of FC (hexane/ethyl acetate=8:2) and crystallisation from diethyl ether/hexane: m.p.=102°-103° C.; Rf (hexane/ethyl acetate=8:2)=0.2; HPLC Rt =18.55 minutes; FAB-MS (M+H)+ =457. The reaction mixture is then partitioned between ethyl acetate and water (2×) and saturated sodium chloride solution (1×) dried over sodium sulfate concentrated