2-methoxycarbonylcyclopentane-1-carboxylic acid

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

Procedure: Cyclopentane-1,2-dicarboxylic acid monomethyl ester (2.21 g, 12.8 mmol), 2-aminoacetonitrile hydrochloride (1.48 g, 16.0 mmol) and benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP) (7.34 g, 14.1 mmol) were dissolved in dimethylformamide (26 mL) and the reaction mixture was cooled to 0° C. Triethylamine (4.9 mL, 35 mmol) was added and the reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was partitioned between water (150 mL) and ethyl acetate (100 mL). The product was extracted into ethyl acetate, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on silica gel with 3:2 ethyl acetate:hexanes eluent to give methyl trans-2-{[(cyanomethyl)amino]carbonyl}cyclopentanecarboxylate as a colorless solid. The reaction mixture was partitioned between water (150 mL) and ethyl acetate (100 mL) The product was extracted into ethyl acetate washed with saturated sodium chloride aqueous solution dried over anhydrous sodium sulfate concentrated The residue was chromatographed on silica gel with 3:2 ethyl acetate

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cyclopentane-1,2-dicarboxylic acid dimethyl ester (2.50 g, 13.4 mmol) was dissolved in methanol (2.5 mL) and a solution of potassium hydroxide (85% purity) (920 mg, 13.9 mmol) in methanol (4.0 mL) and water (0.5 mL) in a 25 mL round bottom flask. The reaction mixture was heated at 75° C. for 4 h. The reaction mixture was cooled to 0° C. and acidified to pH 2 with 2M HCl in water. The reaction mixture was diluted with water (100 mL) and extracted with ether. The organic layer was dried over anhydrous magnesium sulfate and concentrated on a rotary evaporator to give cyclopentane-1,2-dicarboxylic acid monomethyl ester as a faint-yellow liquid. The reaction mixture was cooled to 0° C. extracted with ether The organic layer was dried over anhydrous magnesium sulfate concentrated on a rotary evaporator