2-azidoacetyl chloride

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

Procedure: A solution of p-nitrobenzyl (5R,6S)-2-amino-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (35 mg, 0.1 mmol) in anhydrous tetrahydrofuran (2 ml) is cooled to -25° C. and treated with 4-dimethylaminopyridine (15.9 mg, 0.13 mmol) and, dropwise over 5 minutes, with a solution of 2-azidoacetyl chloride (14.3 mg, 0.12 mmol) in tetrahydrofuran (0.5 ml). The resulting mixture is stirred under a nitrogen atmosphere at 0° C. for 4 hours. The mixture is diluted with ethyl acetate, washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and evaporated under vacuum. The residue is chromatographed on a silica gel thin layer preparative plate to afford the title compound. washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered evaporated under vacuum The residue is chromatographed on a silica gel thin layer preparative plate

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

Procedure: p-Nitrobenzyl 5-hydroxy-5-acetoxymethyl-5,6-dihydro-4H-1,3-thiazine-4-carboxylate (1.27 g., 3.45 mMol) and Et3N (0.58 ml., 4.16 mMol) in anhydrous CH2Cl2 (50 ml.) is stirred under a N2 atomsphere at room temperature while a solution of N3CH2COCl (0.36 ml., 4.13 mMol) in anhydrous CH2Cl2 (20 ml.) is added dropwise over 90 min. After stirring 30 more min., the solution is washed twice with H2O and brine, dried with MgSO4, filtered, and evaporated in vacuo. The residual oil us chromatographed on a column of Baker silica gel. Elution with 3:1 PhH-EtOAc yields p-nitrobenzyl 7α-azido-3-hydroxy-3-acetoxymethyl-cepham-4-carboxylate. is added dropwise over 90 min , the solution is washed twice with H2O and brine dried with MgSO4 filtered evaporated in vacuo The residual oil us chromatographed on a column of Baker silica gel Elution with 3:1 PhH-EtOAc

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

Procedure: p-Nitrobenzyl 5-hydroxy-5-acetoxymethyl-5,6-dihydro-4H-1,3-thiazine-4-carboxylate (1.27 g., 3.45 mMol) and Et3N (0.58 ml., 4.16 mMol) in anhydrous CH2Cl2 (50 ml.) is stirred under a N2 atomsphere at room temperature while a solution of N3CH2COCl (0.36 ml., 4.13 mMol) in anhydrous CH2Cl2 (20 ml.) is added dropwise over 90 min. After stirring 30 more min., the solution is washed twice with H2O and brine, dried with MgSO4, filtered, and evaporated in vacuo. The residual oil us chromatographed on a column of Baker silica gel. Elution with 3:1 PhH-EtOAc yields p-nitrobenzyl 7α-azido-3-hydroxy-3-acetoxymethyl-cepham-4-carboxylate. is added dropwise over 90 min , the solution is washed twice with H2O and brine dried with MgSO4 filtered evaporated in vacuo The residual oil us chromatographed on a column of Baker silica gel Elution with 3:1 PhH-EtOAc

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

Procedure: A solution of p-nitrobenzyl (5R,6S)-2-amino-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (35 mg, 0.1 mmol) in anhydrous tetrahydrofuran (2 ml) is cooled to -25° C. and treated with 4-dimethylaminopyridine (15.9 mg, 0.13 mmol) and, dropwise over 5 minutes, with a solution of 2-azidoacetyl chloride (14.3 mg, 0.12 mmol) in tetrahydrofuran (0.5 ml). The resulting mixture is stirred under a nitrogen atmosphere at 0° C. for 4 hours. The mixture is diluted with ethyl acetate, washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and evaporated under vacuum. The residue is chromatographed on a silica gel thin layer preparative plate to afford the title compound. washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered evaporated under vacuum The residue is chromatographed on a silica gel thin layer preparative plate

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

Procedure: A solution of 0.84 ml (8.4 mmol) azidoacetyl chloride in 5 ml dry dimethylformamide was added dropwise over 10 minutes in an ice-cooled, thoroughly stirred suspension of 1.25 g (5.55 mmol) 9-(2-hydroxyethoxymethyl)guanine and 0.78 ml (5.55 mmol) triethylamine in 40 ml dry dimethylformamide. After 45 minutes of thorough stirring at 0° C., 0.11 ml (1.1 mmol) azidoacetylchloride in 1 ml dimethylformamide was added, and stirring was continued for 15 minutes. The reaction was stopped by the addition of 15 ml 7% NaHCO3 solution whereupon the mixture was evaporated to dryness in vacuo. The residue was triturated with 20 ml of a mixture of methylene chloride:diethyl ether:ethanol (volume ratio 5:5:1). The solid substance obtained was filtered off, thoroughly washed with cold water and recrystallised from hot water, after treatment with active carbon. 1.02 g (62%) of 9-(2-azidoacetoxyethoxy-methyl)guanine m.p. 175°-177° C. (decomposition) was obtained. MS m/e 308 (M30), 151 (base+H); IR (KBr) 2110 (N3), 1745 (COOR) cm-1 ; UV (phosphate buffer, pH=7) λmax 253 nm (ε 8.42× 103), 270 (sh); TLC Rf 0.27 (CHCl3 --MeOH, 8:2), Rf 0.60 (EtOH--HOAc, 8:2). cooled stirring was continued for 15 minutes was evaporated to dryness in vacuo The residue was triturated with 20 ml of a mixture of methylene chloride The solid substance obtained was filtered off thoroughly washed with cold water recrystallised from hot water

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

Procedure: A solution of p-nitrobenzyl (5R,6S)-2-amino-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (35 mg, 0.1 mmol) in anhydrous tetrahydrofuran (2 ml) is cooled to -25° C. and treated with 4-dimethylaminopyridine (15.9 mg, 0.13 mmol) and, dropwise over 5 minutes, with a solution of 2-azidoacetyl chloride (14.3 mg, 0.12 mmol) in tetrahydrofuran (0.5 ml). The resulting mixture is stirred under a nitrogen atmosphere at 0° C. for 4 hours. The mixture is diluted with ethyl acetate, washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and evaporated under vacuum. The residue is chromatographed on a silica gel thin layer preparative plate to afford the title compound. washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered evaporated under vacuum The residue is chromatographed on a silica gel thin layer preparative plate

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

Procedure: A solution of p-nitrobenzyl (5R,6S)-2-amino-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (35 mg, 0.1 mmol) in anhydrous tetrahydrofuran (2 ml) is cooled to -25° C. and treated with 4-dimethylaminopyridine (15.9 mg, 0.13 mmol) and, dropwise over 5 minutes, with a solution of 2-azidoacetyl chloride (14.3 mg, 0.12 mmol) in tetrahydrofuran (0.5 ml). The resulting mixture is stirred under a nitrogen atmosphere at 0° C. for 4 hours. The mixture is diluted with ethyl acetate, washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and evaporated under vacuum. The residue is chromatographed on a silica gel thin layer preparative plate to afford the title compound. washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered evaporated under vacuum The residue is chromatographed on a silica gel thin layer preparative plate

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

Procedure: To 75 ml. of a solution of N-benzylidene-1(S)-t-butoxycarbonylethylamine (5.07 g., 21.7 mmol) and triethylamine (4.84 g., 47.8 mmol) in methylene chloride, there was gradually added dropwise 75 ml. of a solution of azidoacetyl chloride (5.19 g., 43.5 mmol) in methylene chloride at -78° C. After stirring at -78° C. to room temperature for 14 hours, the reaction mixture was washed with water and then with a saturated saline solution, followed by drying over anhydrous magnesium sulfate. After removal of the solvent by distillation, the residue was subjected to silica gel column chromatography, using hexane-ethyl acetate (3:1) as an eluent, to give 1-(1(S)-t-butoxycarbonylethyl)-3(S)-azido-4(R)-azetidin-2-one (2.68 g., yield: 39%) and 1-(1(S)-t-butoxycarbonylethyl)-3(R)-azido-4(S)-phenylazetidin-2-one (2.82 g., yield: 41%). at -78° C the reaction mixture was washed with water by drying over anhydrous magnesium sulfate After removal of the solvent by distillation

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

Procedure: To 75 ml. of a solution of N-benzylidene-1(S)-t-butoxycarbonylethylamine (5.07 g., 21.7 mmol) and triethylamine (4.84 g., 47.8 mmol) in methylene chloride, there was gradually added dropwise 75 ml. of a solution of azidoacetyl chloride (5.19 g., 43.5 mmol) in methylene chloride at -78° C. After stirring at -78° C. to room temperature for 14 hours, the reaction mixture was washed with water and then with a saturated saline solution, followed by drying over anhydrous magnesium sulfate. After removal of the solvent by distillation, the residue was subjected to silica gel column chromatography, using hexane-ethyl acetate (3:1) as an eluent, to give 1-(1(S)-t-butoxycarbonylethyl)-3(S)-azido-4(R)-azetidin-2-one (2.68 g., yield: 39%) and 1-(1(S)-t-butoxycarbonylethyl)-3(R)-azido-4(S)-phenylazetidin-2-one (2.82 g., yield: 41%). at -78° C the reaction mixture was washed with water by drying over anhydrous magnesium sulfate After removal of the solvent by distillation

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

Procedure: A solution of p-nitrobenzyl (5R,6S)-2-amino-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (35 mg, 0.1 mmol) in anhydrous tetrahydrofuran (2 ml) is cooled to -25° C. and treated with 4-dimethylamino pyridine (15.9 mg, 0.13 mmol) and, dropwise over 5 minutes, with a solution of 2-azidoacetyl chloride (14.3 mg, 0.12 mmol) in tetrahydrofuran (0.5 ml). The resulting mixture is stirred under a nitrogen atmosphere at 0° C. for 4 hours. The mixture is diluted with ethyl acetate, washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and evaporated under vacuum. The residue is chromatographed on a silica gel thin layer preparative plate to afford the title compound. washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered evaporated under vacuum The residue is chromatographed on a silica gel thin layer preparative plate

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

Procedure: A solution of p-nitrobenzyl (5R,6S)-2-amino-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (35 mg, 0.1 mmol) in anhydrous tetrahydrofuran (2 ml) is cooled to -25° C. and treated with 4-dimethylamino pyridine (15.9 mg, 0.13 mmol) and, dropwise over 5 minutes, with a solution of 2-azidoacetyl chloride (14.3 mg, 0.12 mmol) in tetrahydrofuran (0.5 ml). The resulting mixture is stirred under a nitrogen atmosphere at 0° C. for 4 hours. The mixture is diluted with ethyl acetate, washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and evaporated under vacuum. The residue is chromatographed on a silica gel thin layer preparative plate to afford the title compound. washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered evaporated under vacuum The residue is chromatographed on a silica gel thin layer preparative plate

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

Procedure: A solution of p-nitrobenzyl (5R,6S)-2-amino-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (35 mg, 0.1 mmol) in anhydrous tetrahydrofuran (2 ml) is cooled to -25° C. and treated with 4-dimethylaminopyridine (15.9 mg, 0.13 mmol) and, dropwise over 5 minutes, with a solution of 2-azidoacetyl chloride (14.3 mg, 0.12 mmol) in tetrahydrofuran (0.5 ml). The resulting mixture is stirred under a nitrogen atmosphere at 0° C. for 4 hours. The mixture is diluted with ethyl acetate, washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and evaporated under vacuum. The residue is chromatographed on a silica gel thin layer preparative plate to afford the title compound. washed with pH 3 phosphate buffer, water, 5% aqueous sodium bicarbonate and brine dried over magnesium sulfate filtered evaporated under vacuum The residue is chromatographed on a silica gel thin layer preparative plate