diethyl (1R,2R)-cyclopropane-1,2-dicarboxylate

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl carboxylate 3 (16.9 g, 19.3 mmol) was dissolved in 170 ml of 2N NaOH and heated under reflux for 1 h. The solution was stirred for additional 18 h at 22° C. The solution was cooled, adjusted to pH 3 with 2N HCl, saturated with NaCl, and finally extracted with ethyl acetate (2×100 ml). The pooled extracts were dried (Na2SO4), evaporated to dryness, and the white residue was used for the next step without further purification (8.5 g, 79%); mp 175-176° C. 1H-NMR (D2O): δ 1.42 (m, 2H), 2.18 (m, 4H). heated under reflux for 1 h The solution was cooled finally extracted with ethyl acetate (2×100 ml) The pooled extracts were dried (Na2SO4) evaporated to dryness the white residue was used for the next step without further purification (8.5 g, 79%)

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl carboxylate 3 (16.9 g, 19.3 mmol) was dissolved in 170 ml of 2N NaOH and heated under reflux for 1 h. The solution was stirred for additional 18 h at 22° C. The solution was cooled, adjusted to pH 3 with 2N HCl, saturated with NaCl, and finally extracted with ethyl acetate (2×100 ml). The pooled extracts were dried (Na2SO4), evaporated to dryness, and the white residue was used for the next step without further purification (8.5 g, 79%); mp 175-176° C. 1H-NMR (D2O): δ 1.42 (m, 2H), 2.18 (m, 4H). heated under reflux for 1 h The solution was cooled finally extracted with ethyl acetate (2×100 ml) The pooled extracts were dried (Na2SO4) evaporated to dryness the white residue was used for the next step without further purification (8.5 g, 79%)

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl acrylate (99%, 270 g, 1.4 eq.) was added to a solution of 2 (282 g, 1.91 mol) in CHCl3 (1500 mL) at 5° C. Cooling was removed and the reaction was stirred at 22° C. for 12 h. Evaporation of the solvent and excess acrylate left an orange oil, which was vacuum distilled (bp 70-75° C./1 mm) to produce 3 (286 g, 80.6%) as a clear thick oil. 1H NMR (250 MHz, CDCl3) δ4.15 (q, J=7.1, 4H); 2.16 (dd, J=7.5, 5.7, 2H); 1.41 (dd, J=7.5, 5.7, 2H); 0.88 (t, J=7.1, 6H). 13C NMR (62.5 MHz, CDCl3) δ 171.69; 60.96; 22.26; 15.18; 14.08. Cooling was removed Evaporation of the solvent and excess acrylate left an orange oil, which distilled (bp 70-75° C./1 mm)

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl acrylate (99%, 270 g, 1.4 eq.) was added to a solution of 2 (282 g, 1.91 mol) in CHCl3 (1500 mL) at 5° C. Cooling was removed and the reaction was stirred at 22° C. for 12 h. Evaporation of the solvent and excess acrylate left an orange oil, which was vacuum distilled (bp 70-75° C./1 mm) to produce 3 (286 g, 80.6%) as a clear thick oil. 1H NMR (250 MHz, CDCl3) δ4.15 (q, J=7.1, 4H); 2.16 (dd, J=7.5, 5.7, 2H); 1.41 (dd, J=7.5, 5.7, 2H); 0.88 (t, J=7.1, 6H). 13C NMR (62.5 MHz, CDCl3) δ 171.69; 60.96; 22.26; 15.18; 14.08. Cooling was removed Evaporation of the solvent and excess acrylate left an orange oil, which distilled (bp 70-75° C./1 mm)

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl carboxylate 3 (16.9 g, 19.3 mmol) was dissolved in 170 ml of 2N NaOH and heated under reflux for 1 h. The solution was stirred for additional 18 h at 22° C. The solution was cooled, adjusted to pH 3 with 2N HCl, saturated with NaCl, and finally extracted with ethyl acetate (2×100 ml). The pooled extracts were dried (Na2SO4), evaporated to dryness, and the white residue was used for the next step without further purification (8.5 g, 79%); mp 175-176° C. 1H-NMR (D2O): δ 1.42 (m, 2H), 2.18 (m, 4H). heated under reflux for 1 h The solution was cooled finally extracted with ethyl acetate (2×100 ml) The pooled extracts were dried (Na2SO4) evaporated to dryness the white residue was used for the next step without further purification (8.5 g, 79%)

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl acrylate (99%, 270 g, 1.4 eq.) was added to a solution of 2 (282 g, 1.91 mol) in CHCl3 (1500 mL) at 5° C. Cooling was removed and the reaction was stirred at 22° C. for 12 h. Evaporation of the solvent and excess acrylate left an orange oil, which was vacuum distilled (bp 70-75° C./1 mm) to produce 3 (286 g, 80.6%) as a clear thick oil. 1H NMR (250 MHz, CDCl3) δ4.15 (q, J=7.1, 4H); 2.16 (dd, J=7.5, 5.7, 2H); 1.41 (dd, J=7.5, 5.7, 2H); 0.88 (t, J=7.1, 6H). 13C NMR (62.5 MHz, CDCl3) δ 171.69; 60.96; 22.26; 15.18; 14.08. Cooling was removed Evaporation of the solvent and excess acrylate left an orange oil, which distilled (bp 70-75° C./1 mm)

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

Procedure: Add a solution of 0.709 g (17.72 mmol) sodium hydroxide in 7.38 mL ethanol to a solution of (+/−)-trans-cyclopropane-1,2-dicarboxylic acid diethyl ester (3.00 g, 16.11 mmol) in 36.9 mL acetone. Stir at room temperature for 24 hours. Pour reaction mixture into 100 mL water and extract with ethyl acetate (1×70 mL). Acidify the aqueous layer with 5N HCl and concentrate under reduced pressure. Add ethyl acetate and filter the resulting slurry. Concentrate the filtrate under reduced pressure to provide the desired compound (2.26 g, 88.7%). Pour extract with ethyl acetate (1×70 mL) concentrate under reduced pressure Add ethyl acetate and filter the resulting slurry Concentrate the filtrate under reduced pressure

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

Procedure: Add a solution of 0.709 g (17.72 mmol) sodium hydroxide in 7.38 mL ethanol to a solution of (+/−)-trans-cyclopropane-1,2-dicarboxylic acid diethyl ester (3.00 g, 16.11 mmol) in 36.9 mL acetone. Stir at room temperature for 24 hours. Pour reaction mixture into 100 mL water and extract with ethyl acetate (1×70 mL). Acidify the aqueous layer with 5N HCl and concentrate under reduced pressure. Add ethyl acetate and filter the resulting slurry. Concentrate the filtrate under reduced pressure to provide the desired compound (2.26 g, 88.7%). Pour extract with ethyl acetate (1×70 mL) concentrate under reduced pressure Add ethyl acetate and filter the resulting slurry Concentrate the filtrate under reduced pressure

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

Procedure: To a solution of diethyl trans-1,2-cyclopropanedicarboxylate (110 mg, 0.59 mmol) in ethanol (3 mL) is added aqueous 1M NaOH (0.65 mL, 0.65 mmol) and the mixture is stirred at room temperature for 48 hours. To this mixture is added 0.65 mL of aqueous 1M HCl and the solvent is removed under reduced pressure to afford the title compound. the solvent is removed under reduced pressure

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

Procedure: 1N Sodium hydroxide (81 mL, 81.36 mmol) was added to a solution of diethyl trans-cyclopropane-1,2-dicarboxylate (15.15 g, 81.36 mmol) in EtOH (100 mL) at 0° C., and the mixture was stirred at 0° C. for 3 hr. The reaction mixture was concentrated under reduced pressure, 2M hydrochloric acid and NaCl were added thereto, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 5→100% ethyl acetate/hexane) to give trans-2-(ethoxycarbonyl)cyclopropanecarboxylic acid (11.20 g, 70.8 mmol, 87%) as a colorless oil. The reaction mixture was concentrated under reduced pressure, 2M hydrochloric acid and NaCl were added the mixture was extracted with ethyl acetate The organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (solvent gradient; 5→100% ethyl acetate/hexane)

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl carboxylate 3 (16.9 g, 19.3 mmol) was dissolved in 170 ml of 2N NaOH and heated under reflux for 1 h. The solution was stirred for additional 18 h at 22° C. The solution was cooled, adjusted to pH 3 with 2N HCl, saturated with NaCl, and finally extracted with ethyl acetate (2×100 ml). The pooled extracts were dried (Na2SO4), evaporated to dryness, and the white residue was used for the next step without further purification (8.5 g, 79%); mp 175–176° C. 1H-NMR (D2O): δ 1.42 (m, 2H), 2.18 (m, 4H). heated under reflux for 1 h The solution was cooled finally extracted with ethyl acetate (2×100 ml) The pooled extracts were dried (Na2SO4) evaporated to dryness the white residue was used for the next step without further purification (8.5 g, 79%)

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl carboxylate 3 (16.9 g, 19.3 mmol) was dissolved in 170 ml of 2N NaOH and heated under reflux for 1 h. The solution was stirred for additional 18 h at 22° C. The solution was cooled, adjusted to pH 3 with 2N HCl, saturated with NaCl, and finally extracted with ethyl acetate (2×100 ml). The pooled extracts were dried (Na2SO4), evaporated to dryness, and the white residue was used for the next step without further purification (8.5 g, 79%); mp 175-176° C. 1H-NMR (D2O): δ1.42 (m, 2H), 2.18 (m, 4H). heated under reflux for 1 h The solution was cooled finally extracted with ethyl acetate (2×100 ml) The pooled extracts were dried (Na2SO4) evaporated to dryness the white residue was used for the next step without further purification (8.5 g, 79%)