3-oxabicyclo[3.2.0]heptane-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:0.00; pressure:0.00; stir:

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: From 2.3 g of 3,5-bistrifluoromethyl aniline and 1.1 g of cyclobutane-1,2-dicarboxylic anhydride used as starting materials, the title compound was obtained in the same manner as in Example 1.

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

Procedure: From 2.3 g of 3,5-bistrifluoromethyl aniline and 1.1 g of cyclobutane-1,2-dicarboxylic anhydride used as starting materials, the title compound was obtained in the same manner as in Example 1.

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

Procedure: A solution of 4-amino-2-chlorobenzonitrile (1229 mg, 8.06 mmol), 3-oxabicyclo[3.2.0]heptane-2,4-dione (1016 mg, 8.06 mmol) and TEA (1.123 mL, 8.06 mmol) in toluene (10 mL) was stirred at 80° C. for 14 hr. To the reaction mixture was added brine at room temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane), and crystallized from ethyl acetate to give 2-((3-chloro-4-cyanophenyl)carbamoyl)cyclobutanecarboxylic acid (795 mg, 2.85 mmol, 35.4%) as colorless crystals. the mixture was extracted with ethyl acetate The organic layer was washed with water and saturated brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane) crystallized from ethyl acetate

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

Procedure: A solution of 4-amino-2-chlorobenzonitrile (1229 mg, 8.06 mmol), 3-oxabicyclo[3.2.0]heptane-2,4-dione (1016 mg, 8.06 mmol) and TEA (1.123 mL, 8.06 mmol) in toluene (10 mL) was stirred at 80° C. for 14 hr. To the reaction mixture was added brine at room temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane), and crystallized from ethyl acetate to give 2-((3-chloro-4-cyanophenyl)carbamoyl)cyclobutanecarboxylic acid (795 mg, 2.85 mmol, 35.4%) as colorless crystals. the mixture was extracted with ethyl acetate The organic layer was washed with water and saturated brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane) crystallized from ethyl acetate

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

Procedure: A mixture of 3-oxabicyclo[3.2.0]heptane-2,4-dione (1 g), triethylamine (1.36 ml) and MeOH (20 ml) was stirred at room temperature over weekend. The mixture was quenched with 1 M HCl, and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4, and concentrated in vacuo to give the title compound (1.18 g) as a colorless oil. The mixture was quenched with 1 M HCl extracted with EtOAc The organic layer was separated washed with water and brine successively dried over MgSO4 concentrated in vacuo

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

Procedure: A mixture of 3-oxabicyclo[3.2.0]heptane-2,4-dione (1 g), triethylamine (1.36 ml) and MeOH (20 ml) was stirred at room temperature over weekend. The mixture was quenched with 1 M HCl, and extracted with EtOAc. The organic layer was separated, washed with water and brine successively, dried over MgSO4, and concentrated in vacuo to give the title compound (1.18 g) as a colorless oil. The mixture was quenched with 1 M HCl extracted with EtOAc The organic layer was separated washed with water and brine successively dried over MgSO4 concentrated in vacuo