Diethyl cis-cyclopropane-1,2-dicarboxylate

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

Procedure: A stirred mixture of diethyl cis-1,2-cyclopropanedicarboxylate (53.0 g, 284.6 mmol) and sodium hydroxide (32.4 g, 809.1 mmol) in water (200 mL) was heated at reflux for 5 h. The mixture was then allowed to stir at room temperature overnight. The ethanol formed was evaporated under reduced pressure and the remaining aqueous solution was acidified with a slight excess of concentrated aqueous HCl (74.8 mL, 92.8 mmol). The mixture was evaporated to dryness under reduced pressure, and the residue was washed with hot ethyl acetate (3 times with 200 mL). The ethyl acetate layer was separated, dried (MgSO4) and evaporated to dryness under reduced pressure to give 35.5 g of the title compound of Step B as a white solid (96% yield); m.p. 122°-124° C. IR (mineral oil, cm-1), 1691.0 (C=O); 2600-3100, broad (OH). was heated at reflux for 5 h was evaporated under reduced pressure The mixture was evaporated to dryness under reduced pressure the residue was washed with hot ethyl acetate (3 times with 200 mL) The ethyl acetate layer was separated dried (MgSO4) evaporated to dryness under reduced pressure

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

Procedure: To a stirred suspension of 32.8 g (818.8 mmol) of 60% sodium hydride mineral oil dispersion in 200 mL of toluene under nitrogen, was added between 10 to 20 mL of a blend of ethyl acrylate (81.2 g, 810.7 mmol) and ethyl chloroacetate (99.4 g, 810.7 mmol) followed by several drops of ethanol. After an induction period of about 1 h, steady gas and heat evolution began with the reaction mixture temperature reaching 35° C. The remaining mixed ester reagent was carefully added dropwise with ice-bath cooling so as to maintain a reaction temperature of 30°-80° C. After the addition was complete (4 h), the mixture was cooled to room temperature and carefully poured into water (300 mL). The organic layer was separated and dried (MgSO4) and evaporated to a dry residue. The dry residue was chromatographed on silica gel using 10% ethyl acetate in hexane as the eluant. The fractions containing the desired compound were combined and evaporated to dryness under reduced pressure to give 53.0 g of the title compound of Step A as a clear oil (35% yield). IR (neat, cm-1): 1728.9 (C=O); After an induction period of about 1 h, steady gas and heat evolution reaching 35° C was carefully added dropwise with ice-bath cooling so as to maintain a reaction temperature of 30°-80° C After the addition (4 h) The organic layer was separated dried (MgSO4) evaporated to a dry residue The dry residue was chromatographed on silica gel using 10% ethyl acetate in hexane as the eluant The fractions containing the desired compound evaporated to dryness under reduced pressure