3,3,3-trifluoropropanehydrazide

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

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

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

Procedure: To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.25 g, 0.90 mmol) in dry DCM (40 mL) were added 3,3,3-trifluoropropanehydrazide 228 (0.19 g, 1.35 mmol), 1-hydroxybenzotriazole (0.19 g, 1.35 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.26 g, 1.35 mmol) and 4-(dimethylamino)pyridine (0.16 g, 1.35 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was purified by column chromatography to give (2R,5S)-6-(benzyloxy)-7-oxo-N-(3,3,3-trifluoropropanoyl)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide 229 (0.26 g, 72%) as a white solid. concentrated under vacuum The residue was purified by column chromatography

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

Procedure: To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.25 g, 0.90 mmol) in dry DCM (40 mL) were added 3,3,3-trifluoropropanehydrazide 228 (0.19 g, 1.35 mmol), 1-hydroxybenzotriazole (0.19 g, 1.35 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.26 g, 1.35 mmol) and 4-(dimethylamino)pyridine (0.16 g, 1.35 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was purified by column chromatography to give (2R,5S)-6-(benzyloxy)-7-oxo-N-(3,3,3-trifluoropropanoyl)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide 229 (0.26 g, 72%) as a white solid. concentrated under vacuum The residue was purified by column chromatography

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

Procedure: To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.25 g, 0.90 mmol) in dry DCM (40 mL) were added 3,3,3-trifluoropropanehydrazide 228 (0.19 g, 1.35 mmol), 1-hydroxybenzotriazole (0.19 g, 1.35 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.26 g, 1.35 mmol) and 4-(dimethylamino)pyridine (0.16 g, 1.35 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was purified by column chromatography to give (2R,5S)-6-(benzyloxy)-7-oxo-N′-(3,3,3-trifluoropropanoyl)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide 229 (0.26 g, 72%) as a white solid. concentrated under vacuum The residue was purified by column chromatography

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

Procedure: A solution of 3,3,3-trifluoro-propionic acid methyl ester (24.6 g, 173 mmol) in methanol (173 mL) was treated with hydrazine hydrate (8.4 mL, 173 mmol). The resulting mixture was then heated under reflux for 16 h and filtered. The filtrate was adsorbed on silica, evaporated and chromatographed (SiO2, dichloromethane:methanol=95:5 to 90:10). The title compound (14.2 g, 58%) was obtained as a white solid. MS: m/e=142.1 [M]+. The resulting mixture was then heated under reflux for 16 h filtered evaporated chromatographed (SiO2, dichloromethane:methanol=95:5 to 90:10)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of tert-butyl(1-(4-(7-phenyl-2-thioxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutyl)carbamate (250 mg, 0.513 mmol) and 3,3,3-trifluoropropanehydrazide (145 mg, 1.205 mmol) in p-xylene (2 ml) was heated to 150° C. for 15 minutes under microwave irradiation. The resulting reaction mixture was concentrated to dryness under reduced pressure and purified by Biotage silica gel chromatography (gradient 0% to 20% ethyl acetate in n-hexanes) to give the title compound (38 mg, 13%). LCMS (Method D): RT=1.499 min, M+1=578. 1H NMR (500 MHz, CDCl3): 7.84 (1H, s), 7.36-7.32 (5H, m), 7.31-7.28 (2H, m), 7.23-7.18 (2H, m), 5.60 (2H, s), 4.12 (2H, q), 2.52-2.42 (4H, m), 2.12-2.01 (1H, m), 1.87-1.78 (1H, m), 1.44-1.26 (9H, bs). The resulting reaction mixture was concentrated to dryness under reduced pressure purified by Biotage silica gel chromatography (gradient 0% to 20% ethyl acetate in n-hexanes)

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

Procedure: Ethyl-3,3,3-trifluoropropanoate (2.5 g, 0.016 mol) and hydrazine monohydrate (1.2 g, 0.024 mol) were heated to reflux for 1 hour. The reaction mixture was concentrated under reduced pressure and the residue was treated with toluene (100 ml×3) to azeotrope hydrazine in excess. to reflux for 1 hour The reaction mixture was concentrated under reduced pressure the residue was treated with toluene (100 ml×3)

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

Procedure: To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.25 g, 0.90 mmol) in dry DCM (40 mL) were added 3,3,3-trifluoropropanehydrazide 228 (0.19 g, 1.35 mmol), 1-hydroxybenzotriazole (0.19 g, 1.35 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.26 g, 1.35 mmol) and 4-(dimethylamino)pyridine (0.16 g, 1.35 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was purified by column chromatography to give (2R,5S)-6-(benzyloxy)-7-oxo-N-(3,3,3-trifluoropropanoyl)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide 229 (0.26 g, 72%) as a white solid. concentrated under vacuum The residue was purified by column chromatography