diethyl 2-(cyclopropylmethyl)propanedioate

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

Procedure: A solution of NaOEt in EtOH (2.7 M, 2.6 mL, 6.9 mmol) is cooled at 0° C. and diethylmalonate (0.95 mL, 6.2 mmol) is added with another 1.5 mL of EtOH. Bromo methyl cyclopropane (0.67 mL, 6.9 mmol) is subsequently added. The resulting mixture is allowed to reach room temperature and stirred overnight. The mixture is then quenched with water and extracted with ether. The organic phase is dried and evaporated to give the desired product that is used as such. to reach room temperature The mixture is then quenched with water extracted with ether The organic phase is dried evaporated

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

Procedure: A solution of NaOEt in EtOH (2.7 M, 2.6 mL, 6.9 mmol) is cooled at 0° C. and diethylmalonate (0.95 mL, 6.2 mmol) is added with another 1.5 mL of EtOH. Bromo methyl cyclopropane (0.67 mL, 6.9 mmol) is subsequently added. The resulting mixture is allowed to reach room temperature and stirred overnight. The mixture is then quenched with water and extracted with ether. The organic phase is dried and evaporated to give the desired product that is used as such. to reach room temperature The mixture is then quenched with water extracted with ether The organic phase is dried evaporated

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

Procedure: A solution of NaOEt in EtOH (2.7 M, 2.6 mL, 6.9 mmol) is cooled at 0° C. and diethylmalonate (0.95 mL, 6.2 mmol) is added with another 1.5 mL of EtOH. Bromo methyl cyclopropane (0.67 mL, 6.9 mmol) is subsequently added. The resulting mixture is allowed to reach room temperature and stirred overnight. The mixture is then quenched with water and extracted with ether. The organic phase is dried and evaporated to give the desired product that is used as such. to reach room temperature The mixture is then quenched with water extracted with ether The organic phase is dried evaporated

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

Procedure: To an ice-cooled solution of 2-cyclopropylmethylmalonic acid diethyl ester (1.3 g, 6.067 mmol) in THF (45 mL) was added, portionwise, sodium hydride (0.485 g, 60% in oil, 12.13 mmol). The mixture was stirred in the ice bath for 15 min, and then at RT for 15 min. The suspension was re-cooled in the ice bath and NBS (1.19 g, 6.67 mmol) was added over 5 min. The mixture was stirred in the ice bath for 10 min, and then at RT for 30 min. The reaction mixture was filtered through Celite® and the filtrate concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% EtOAc in cyclohexane) affording the title compound as a colourless oil (1.55 g, 87%). 1H NMR (CDCl3, 300 MHz): δ 4.33-4.22 (4H, m), 2.24 (2H, d, J=6.6 Hz) 1.30 (6H, d, J=7.1 Hz) 1.01-0.88 (1H, m), 0.54-0.48 (2H, m), 0.17-0.12 (2H, m). was added was added over 5 min at RT for 30 min The reaction mixture was filtered through Celite® the filtrate concentrated in vacuo The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% EtOAc in cyclohexane)

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

Procedure: To an ice-cooled solution of diethyl malonate (3.0 g, 18.7 mmol) in THF (30 mL) was added, portionwise over 15 min, sodium hydride (0.824 g, 60% in oil, 20.6 mmol). The mixture was stirred at RT for 30 min, and then cooled in an ice bath. Cyclopropylmethyl bromide (2.36 mL, 24.3 mmol) was added and the reaction mixture stirred at RT for 1 h and then refluxed for 6 h. The cooled mixture was concentrated in vacuo, the residue was partitioned between diethyl ether and dilute aqueous NH4Cl; and the aqueous phase was extracted with diethyl ether. The combined organic phases were washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% EtOAc in cyclohexane) affording a mixture of the title compound and 2-but-3-enylmalonic acid diethyl ester (3.24 g, 10:1 ratio respectively). This mixture was dissolved in DCM (150 mL) and a solution of mCPBA (0.77 g, 4.46 mmol) in DCM (5 mL) added. The reaction mixture was stirred at RT for 16 h, and then washed with a saturated solution of NaHCO3, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% EtOAc in cyclohexane) affording the title compound as a colourless oil (2.68 g, 67%). 1H NMR (CDCl3, 300 MHz): δ 4.20 (4H, q, J=7.1 Hz), 3.44 (1H, t, J=7.5 Hz), 1.81 (2H, t, J=7.3 Hz), 1.27 (6H, t, J=7.1 Hz), 0.80-0.67 (1H, m), 0.48-0.42 (2H, m), 0.12-0.07 (2H, m). was added, portionwise over 15 min cooled in an ice bath the reaction mixture stirred at RT for 1 h refluxed for 6 h The cooled mixture was concentrated in vacuo the residue was partitioned between diethyl ether and dilute aqueous NH4Cl and the aqueous phase was extracted with diethyl ether The combined organic phases were washed with brine dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% EtOAc in cyclohexane) affording

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

Procedure: A solution of NaOEt in EtOH (2.7 M, 2.6 mL, 6.9 mmol) is cooled at 0° C. and diethylmalonate (0.95 mL, 6.2 mmol) is added with another 1.5 mL of EtOH. Bromo methyl cyclopropane (0.67 mL, 6.9 mmol) is subsequently added. The resulting mixture is allowed to reach room temperature and stirred overnight. The mixture is then quenched with water and extracted with ether. The organic phase is dried and evaporated to give the desired product that is used as such. to reach room temperature The mixture is then quenched with water extracted with ether The organic phase is dried evaporated