3-benzyl-3-azabicyclo[3.1.0]hexane-2,4-dione

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

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

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-benzyl-3-azabicyclo[3.1.0]hexane-2,4-dione (Prepared as per U.S. Pat. No. 4,183,857, 1.9 gm, 9.5 mmol) was dissolved in 100 ml of tetrahydrofuran and cooled to −78° C. Methyllithium (10.5 ml of a 0.98M solution in ether, 10.2 mmol) was added dropwise. Saturated aqueous ammonium chloride was added to the cold reaction mixture. The mixture was then extracted with ethyl acetate. The combined organic layers were dried over sodium sulphate, filtered and concentrated in vacuo to provide the title compound. The mixture was then extracted with ethyl acetate The combined organic layers were dried over sodium sulphate filtered concentrated in vacuo

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

Procedure: 1,2-cyclopropanedicarboxylic acid is treated with benzylamine to form 3-(benzyl)-3-azabicyclo(3.1.0)hexane-2,4-dione (I).

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

Procedure: 1,2-cyclopropanedicarboxylic acid is treated with benzylamine to form 3-(benzyl)-3-azabicyclo(3.1.0)hexane-2,4-dione (I).

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-benzyl-3-azabicyclo[3.1.0]hexane-2,4-dione(U.S. Pat. No. 4,183,857, 1.9 gm, 9.5 mmol) was dissolved in 100 ml of tetrahydrofuran and cooled to −78° C. Methyllithium (10.5 ml of a 0.98M solution in ether, 10.2 mmol) was added dropwise. Saturated aqueous ammonium chloride was added to the cold reaction mixture; the mixture was then extracted with ethyl acetate. The combined organic layers were dried over sodium sulphate, filtered and concentrated in vacuo to provide the title compound. the mixture was then extracted with ethyl acetate The combined organic layers were dried over sodium sulphate filtered concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-benzyl-3-azabicyclo[3.1.0]hexane-2,4-dione(U.S. Pat. No. 4,183,857, 1.9 gm, 9.5 mmol) was dissolved in 100 ml of tetrahydrofuran and cooled to −78° C. Methyllithium (10.5 ml of a 0.98M solution in ether, 10.2 mmol) was added dropwise. Saturated aqueous ammonium chloride was added to the cold reaction mixture; the mixture was then extracted with ethyl acetate. The combined organic layers were dried over sodium sulphate, filtered and concentrated in vacuo to provide the title compound. the mixture was then extracted with ethyl acetate The combined organic layers were dried over sodium sulphate filtered concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-benzyl-3-azabicyclo[3.1.0]hexane-2,4-dione(U.S. Pat. No. 4,183,857, 1.9 gm, 9.5 mmol) was dissolved in 100 ml of tetrahydrofuran and cooled to −78° C. Methyllithium (10.5 ml of a 0.98M solution in ether, 10.2 mmol) was added dropwise. Saturated aqueous ammonium chloride was added to the cold reaction mixture; the mixture was then extracted with ethyl acetate. The combined organic layers were dried over sodium sulphate, filtered and concentrated in vacuo to provide the title compound. the mixture was then extracted with ethyl acetate The combined organic layers were dried over sodium sulphate filtered concentrated in vacuo

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

Procedure: 3-oxabicyclo[3.1.0]hexane-2,4-dione (23-1) (20 g, 0.179 mol) was dissolved in acetic acid (100 mL), and benzylamine (28.8 g, 0.269 mol) was added dropwise under cooling in a water bath, after the completion of addition, the temperature was raised to reflux and stirred overnight. The reaction mixture was cooled to room temperature, poured into 1 L of water to precipitate large amount of white solid, filtered, and the filter cake was recrystallized from isopropanol to give Compound 23-2 (27 g). under cooling in a water bath after the completion of addition the temperature was raised to reflux to precipitate large amount of white solid filtered the filter cake was recrystallized from isopropanol

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 63.2 g (0.486 mol) of 1 was added in portions to 150 ml of thionyl chloride. The mixture was refluxed for 1 hour, then was stripped. The residue was distilled to give cis-1,2-cyclopropanedicarboxylic acid anhydride (3A) bp 134° C. (10 Torr.). 2.14 g (0.02 mol) of benzylamine was carefully added to 2.24 g (0.02 mol) of 3A (CAUTION: THE REACTION IS VERY EXOTHERMIC.) The mixture was heated at 180° C. for 2 hours. After cooling, the residue was recrystallized from isopropyl alcohol to give 3-(benzyl)-3-azabicyclo(3.1.0)hexane-2,4-dione, as white needles, mp 90°-91° C. (3B). A cooled (0°) solution of 305 ml (1.09 mol) of 70% sodium bis(2-methoxyethoxy)aluminum hydride in benzene diluted with 600 ml of ether was treated with 48.7 g (0.24 mole) of 3B. The mixture was stirred at 0° for 1/2 hr and refluxed for 3 hrs. After standing at room temperature overnight, excess metal hydride was destroyed by cautiously adding cold water. The mixture was filtered after addition of diatomaceous silica (Celite). The ether layer was removed and the aqueous layer was extracted with ether. The combined organic layers were dried (MgSO4). Ether and 2-methoxyethanol were evaporated under reduced pressure to give 3, as an oil. Distillation gave 3, bp: 79°-80° C. (0.01 Torr.). After cooling the residue was recrystallized from isopropyl alcohol

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

Procedure: 1,2-cyclopropanedicarboxylic acid is treated with benzylamine to form 3-(benzyl)-3-azabicyclo(3.1.0)hexane-2,4-dione (I).