methyl cyclopropanecarboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:

Conditions: temp:90.01; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium ethoxide (8 g, 117.64 mmol) was added to a solution of cyclopropyl methyl ketone (5 g, 59.4 mmol) and methyl cyclopropane carboxylate (12 ml, 118.9 mmol) in DMSO (30 mL). The resulting mixture was heated at 60° C. overnight and then cooled to 0° C. After quenching the reaction with 6N HCl, work-up (H2O/AcOEt) gave the title compound as a brown liquid which was used without any purification. 1H-NMR (δ ppm, CDCl3, 400 MHz): 16.05 (bs, 0.6H), 5.72 (s, 0.6H) 3.78 (s, 0.8H), 2.08-2.0 (m, 0.8H), 1.62-1.53 (m, 1.2H), 1.12-1.05 (m, 4H), 0.97-0.83 (m, 4H). MS (m/z): 153.2 [M+H]+. cooled to 0° C After quenching the reaction with 6N HCl, work-up (H2O/AcOEt)

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of sodium hexamethyldisilazide (4.2 mL, 1.0 M in THF) at 0° C. was added a solution of the compound prepared in step 2 (0.78 g, 0.002 mol) in 10 mL of dry THF dropwise. The dark brown solution was stirred at this temperature for 30 minutes. Then a solution of methyl cyclopropanecarboxylate (0.27 g, 0.0026 mol) in 5 mL of dry THF was added. The reaction mixture was allowed to warm up to room temperature and stirred for 3 hours. Water was added and the aqueous phase was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated and purified by chromatography on silica gel (ethyl acetate/hexane, 3:7) to give 0.30 g of product, 5-cyclopropyl-1-[2-[[(1,1-dimethylethyl) dimethylsilyl]oxy]ethyl]-3,4-diphenyl-1H-pyrazole, as a light yellow oil (35% yield), 1H NMR (CDCL3): δ8.53 (m, 2H), 7.32 (m, 2H), 7.14 (d, J=5.6 Hz, 2H), 6.97 (m, 2H),.4.47 (t, J=4.8 Hz, 2H), 4.14 (t, J=4.8 Hz. 2H), 1.93 (m, 1H), 0.95 (m, 2H), 0.87 (s, 9H), 0.41 (m, 2H); Anal. Calc'd For C25H32FN3OSi: C, 68.61; H, 7.37; N, 9.60. Found: C, 68.39; H, 7.81; N, 9.23. stirred for 3 hours the aqueous phase was extracted with ethyl acetate The organic layer was washed with brine dried over magnesium sulfate filtered The filtrate was concentrated purified by chromatography on silica gel (ethyl acetate/hexane, 3:7)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methylcyclopropanecarboxylate (20.2 ml, 286.3 mmol) was added to a stirred solution of 1-cyclopropylethanone (9 ml, 152.4 mmol) in dimethylsulfoxide (25 ml). Sodium methoxide powder (10.8 g, 200 mmol) was added, and the reaction was stirred at 55° C. for 8 hours. The mixture was cooled, diluted with toluene, neutralised with 6M hydrochloric acid, and then extracted with toluene. The combined extracts were washed with sodium carbonate, dried over magnesium sulphate and evaporated in vacuo to provide the title compound (14.9 g, 78%) as a mixture 2:1 enol:ketone forms. 1H NMR (CDCl3, 400 MHz): δ=0.79-0.87 (m, 4H), 0.98-1.01 (m, 4H), 1.46-1.51 (m, 2H-enol), 1.93-1.97 (m, 2H-keto), 3.70 (s, 2H-keto), 5.65 (s, 1H-enol); LRMS: APCl+: m/z 153 [MH+]; APCl− m/z 151 [M−H]−. The mixture was cooled extracted with toluene The combined extracts were washed with sodium carbonate dried over magnesium sulphate evaporated in vacuo

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methylcyclopropanecarboxylate (20.2 ml, 286.3 mmol) was added to a stirred solution of 1-cyclopropylethanone (9 ml, 152.4 mmol) in dimethylsulfoxide (25 ml). Sodium methoxide powder (10.8 g, 200 mmol) was added, and the reaction was stirred at 55° C. for 8 hours. The mixture was cooled, diluted with toluene, neutralised with 6M hydrochloric acid, and then extracted with toluene. The combined extracts were washed with sodium carbonate, dried over magnesium sulphate and evaporated in vacuo to provide the title compound (14.9 g, 78%) as a mixture 2:1 enol:ketone forms. 1H NMR (CDCl3, 400 MHz): δ=0.79-0.87 (m, 4H), 0.98-1.01 (m, 4H), 1.46-1.51 (m, 2H-enol), 1.93-1.97 (m, 2H-keto), 3.70 (s, 2H-keto), 5.65 (s, 1H-enol); LRMS: APCl+: m/z 153 [MH+]; APCl− m/z 151 [M−H]−. The mixture was cooled extracted with toluene The combined extracts were washed with sodium carbonate dried over magnesium sulphate evaporated in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium ethoxide (8 g, 117.64 mmol) was added to a solution of cyclopropyl methyl ketone (5 g, 59.4 mmol) and methyl cyclopropane carboxylate (12 ml, 118.9 mmol) in DMSO (30 mL). The resulting mixture was heated at 60° C. overnight and then cooled to 0° C. After quenching the reaction with 6N HCl, work-up (H2O/AcOEt) gave the title compound as a brown liquid which was used without any purification. 1H-NMR (δ ppm, CDCl3, 400 MHz): 16.05 (bs, 0.6H), 5.72 (s, 0.6H) 3.78 (s, 0.8H), 2.08-2.0 (m, 0.8H), 1.62-1.53 (m, 1.2H), 1.12-1.05 (m, 4H), 0.97-0.83 (m, 4H). MS (m/z): 153.2 [M+H]+. cooled to 0° C After quenching the reaction with 6N HCl, work-up (H2O/AcOEt)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium ethoxide (8 g, 117.64 mmol) was added to a solution of cyclopropyl methyl ketone (5 g, 59.4 mmol) and methyl cyclopropane carboxylate (12 ml, 118.9 mmol) in DMSO (30 mL). The resulting mixture was heated at 60° C. overnight and then cooled to 0° C. After quenching the reaction with 6N HCl, work-up (H2O/AcOEt) gave the title compound as a brown liquid which was used without any purification. 1H-NMR (δ ppm, CDCl3, 400 MHz): 16.05 (bs, 0.6H), 5.72 (s, 0.6H) 3.78 (s, 0.8H), 2.08-2.0 (m, 0.8H), 1.62-1.53 (m, 1.2H), 1.12-1.05 (m, 4H), 0.97-0.83 (m, 4H). MS (m/z): 153.2 [M+H]+. cooled to 0° C After quenching the reaction with 6N HCl, work-up (H2O/AcOEt)

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

Procedure: To a solution of sodium hexamethyldisilazide (4.2 mL, 1.0 M in THF) at 0° C. was added absolution of the compound prepared in step 2 (0.78 g, 0.002 mol) in 10 mL of dry THF dropwise. The dark brown solution was stirred at this temperature for 30 minutes. Then a solution of methyl cyclopropanecarboxylate (0.27 g, 0.0026 mol) in 5 mL of dry THF was added. The reaction mixture was allowed to warm up to room temperature and stirred for 3 hours. Water was added and the aqueous phase was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated and purified by chromatography on silica gel (ethyl acetate/hexane, 3:7) to give 0.30 g of product, 5-cyclopropyl-1-[2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethyl]-3,4-diphenyl-1H-pyrazole, as a light yellow oil (35% yield), 1H NMR (CDCL3): δ 8.53 (m, 2H), 7.32 (m, 2H), 7.14 (d, J=5.6 Hz, 2H), 6.97 (m, 2H), 4.47 (t, J=4.8 Hz, 2H), 4.14 (t, J=4.8 Hz, 2H), 1.93 (m, 1H), 0.95 (m, 2H), 0.87 (s, 9H), 0.41(m, 2H); Anal. Calc'd For C25H32FN3OSi: C, 68.61; H, 7.37; N, 9.60. Found: C, 68.39; H, 7.81; N, 9.23. stirred for 3 hours the aqueous phase was extracted with ethyl acetate The organic layer was washed with brine dried over magnesium sulfate filtered The filtrate was concentrated purified by chromatography on silica gel (ethyl acetate/hexane, 3:7)