bicyclo[3.1.0]hexan-3-one

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

Procedure: Bicyclo[3.1.0]hexan-3-one (192 mg, 2.0 mmol) was reacted with POCl3, (0.33 mL, 3.6 mmol) and dry DMF (0.31 mL, 4.0 mmol) in dry CH2Cl2 (0.3 mL) according to General Procedure 1.1.A. The material was purified by passing through a pad of silica gel eluting with Et2O to afford the title compound. The material was used as is in the next step. The material was purified

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of bicyclo[3.1.0]hexan-3-one (0.30 g, 3.12 mmol) and diethyl oxalate (0.433 mL, 3.20 mmol) in denatured absolute ethanol (10 mL) was added a 1.0 M THF solution of potassium tert-butoxide (3.28 mL, 3.28 mmol). The resulting yellow solution was stirred at 20° C. for 2 h. (2,4-Difluorophenyl)hydrazine hydrochloride (0.564 g, 3.12 mmol) was added followed by a 3.0 M aqueous solution of hydrogen chloride (3.12 mL, 9.36 mmol). The reaction was stirred at 40° C., for 18 h. Brine (100 mL) was added. The mixture was extracted with dichloromethane (3×25 mL). The combined organic extracts were dried over MgSO4, filtered, then concentrated under reduced pressure. The residue was purified by silica gel flash chromatography to give a mixture of the title compound (0.672 g) and 1-(2,4-difluoro-phenyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole-3-carboxylic acid methyl ester (0.090 g) as yellow solids. LCMS m/z=305.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 0.36 (td, J=4.5, 3.8 Hz, 1H), 1.17 (td, J=7.9, 5.0 Hz, 1H), 1.41 (t, J=7.2 Hz, 3H), 2.09-2.16 (m, 1H), 2.33-2.37 (m, 1H), 2.80 (d, J=16.9 Hz, 1H), 2.98 (dd, J=16.9, 6.7 Hz, 1H), 4.36-4.49 (m, 2H), 6.92-6.99 (m, 2H), 7.61-7.67 (m, 1H). was added The mixture was extracted with dichloromethane (3×25 mL) The combined organic extracts were dried over MgSO4 filtered concentrated under reduced pressure The residue was purified by silica gel flash chromatography to give

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

Procedure: Bicyclo[3.1.0]hexan-3-one (192 mg, 2.0 mmol) was reacted with POCl3, (0.33 mL, 3.6 mmol) and dry DMF (0.31 mL, 4.0 mmol) in dry CH2Cl2 (0.3 mL) according to General Procedure 1.1.A. The material was purified by passing through a pad of silica gel eluting with Et2O to afford the title compound. The material was used as is in the next step. The material was purified