1,1-二氟-4-亚甲基环己烷

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution from EXAMPLE 302D was added water (75 mL), then N-methylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product. The solution was cooled to room temperature The solution was then extracted three times with ethyl acetate washed with 1M HCl, and brine concentrated The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes 5% methanol in ethyl acetate to give the product

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution from EXAMPLE 302D was added water (75 mL), then N-methylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product. The solution was cooled to room temperature The solution was then extracted three times with ethyl acetate washed with 1M HCl, and brine concentrated The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes 5% methanol in ethyl acetate to give the product

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution from EXAMPLE 302D was added water (75 mL), then N-methylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product. The solution was cooled to room temperature The solution was then extracted three times with ethyl acetate washed with 1M HCl, and brine concentrated The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes 5% methanol in ethyl acetate to give the product

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution from EXAMPLE 302D was added water (75 mL), then N-methylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product. The solution was cooled to room temperature The solution was then extracted three times with ethyl acetate washed with 1M HCl, and brine concentrated The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes 5% methanol in ethyl acetate to give the product

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution from EXAMPLE 490A was added water (75 mL), then N-metthylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M aqueous HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product. The solution was cooled to room temperature The solution was then extracted three times with ethyl acetate washed with 1M aqueous HCl, and brine concentrated The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes 5% methanol in ethyl acetate to give the product

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution from EXAMPLE 302D was added water (75 mL), then N-methylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product. The solution was cooled to room temperature The solution was then extracted three times with ethyl acetate washed with 1M HCl, and brine concentrated The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes 5% methanol in ethyl acetate to give the product

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution from EXAMPLE 490A was added water (75 mL), then N-methylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M aqueous HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product. The solution was cooled to room temperature The solution was then extracted three times with ethyl acetate washed with 1M aqueous HCl, and brine concentrated The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes 5% methanol in ethyl acetate to give the product

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A methyl triphenyl phosphonium bromide/sodium amide mixture (MTP instant ylide, 0.49 g, 1.24 mmol) was suspended in anhydrous Et2O (3 mL) stirring for 1 h at r.t. Afterwards, the reaction mixture was cooled at 0° C. and a solution of 4,4-difluorocyclohexanone (0.145 g, 1.08 mmol) in 3 mL of Et2O was added dropwise into. Stirring at r.t. was maintained for 16 h, then the reaction mixture was filtered and the filtrate was used in the next step without further purification. Afterwards, the reaction mixture was cooled at 0° C. Stirring at r.t. was maintained for 16 h the reaction mixture was filtered the filtrate was used in the next step without further purification

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution from EXAMPLE 302D was added water (75 mL), then N-methylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product. The solution was cooled to room temperature The solution was then extracted three times with ethyl acetate washed with 1M HCl, and brine concentrated The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes 5% methanol in ethyl acetate to give the product

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution from EXAMPLE 490A was added water (75 mL), then N-metthylmorpholine-N-oxide (6.4 mL, 50% solution in water) and OsO4 (14.2 g, 2.5 wt % solution in tert-butanol) were added, and the reaction was stirred for 96 hours at 50° C. The solution was cooled to room temperature, treated with saturated aqueous Na2S2O3 solution (100 mL) for 30 minutes, and then acidified with concentrated aqueous HCl. The solution was then extracted three times with ethyl acetate, and the organic layers were combined, washed with 1M aqueous HCl, and brine, and concentrated. The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes, and then 5% methanol in ethyl acetate to give the product. The solution was cooled to room temperature The solution was then extracted three times with ethyl acetate washed with 1M aqueous HCl, and brine concentrated The crude mixture was chromatographed on silica gel using 10-100% ethyl acetate in hexanes 5% methanol in ethyl acetate to give the product