(2,2-difluorocyclopropyl)methanol

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

Procedure: Methanesulfonyl chloride (1.43 mL) was added to a solution of (2,2-difluorocyclopropyl)methanol (1.00 g) and triethylamine (2.58 mL) in THF (10 mL) dropwise at 0° C. The mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.47 g) as a colorless oil. the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate concentrated in vacuo The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: Prepared analogously to example XII.1 using (2,2-difluorocyclopropyl)methanol and 2-fluoro-3-nitro-pyridine

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 307 mg (2.84 mmol) (2,2-difluorocyclopropyl)methanol in 1,4-dioxane (10 mL) is added 69 mg (2.84 mmol) sodium hydride and 500 mg (2.84 mmol) 2-bromo-6-fluoropyridine. The mixture is stirred for 2 h at 90° C. Water and DMF are added and the mixture is filtered and concentrated in vacuo. The residue is purified by HPLC (C18 RP Sunfire, acetonitrile/water (+0.1% TFA)) to yield the desired product. the mixture is filtered concentrated in vacuo The residue is purified by HPLC (C18 RP Sunfire, acetonitrile/water (+0.1% TFA))

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 307 mg (2.84 mmol) (2,2-difluorocyclopropyl)methanol in 1,4-dioxane (10 mL) is added 69 mg (2.84 mmol) sodium hydride and 500 mg (2.84 mmol) 2-bromo-6-fluoropyridine. The mixture is stirred for 2 h at 90° C. Water and DMF are added and the mixture is filtered and concentrated in vacuo. The residue is purified by HPLC (C18 RP Sunfire, acetonitrile/water (+0.1% TFA)) to yield the desired product. the mixture is filtered concentrated in vacuo The residue is purified by HPLC (C18 RP Sunfire, acetonitrile/water (+0.1% TFA))

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

Procedure: Using N-((2S)-1-((2-(4-(benzyloxy)-3,5-difluorophenyl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)acetamide and (2,2-difluorocyclopropyl)methanol, and in the same manner as in Step A and Step B of Example 4, the title compound was obtained.

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

Procedure: To a solution of (2,2-difluorocyclopropyl)methanol (20.0 g) and triethylamine (32.2 mL) in THF (300 mL) was added 4-nitrobenzenesulfonyl chloride (41.0 g) at 0° C., and the mixture was stirred for 4 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (47.2 g) as a white solid. the mixture was extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: Using 6-chloronicotinic acid and 2,2-difluorocyclopropanemethanol, and in the same manner as in Step A of Example 40, the title compound was obtained.

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

Procedure: Using 6-chloronicotinic acid and 2,2-difluorocyclopropanemethanol, and in the same manner as in Step A of Example 40, the title compound was obtained.

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

Procedure: Using 6-chloronicotinic acid and 2,2-difluorocyclopropanemethanol, and in the same manner as in Step A of Example 40, the title compound was obtained.

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

Procedure: Using N-((2S)-1-((2-(4-(benzyloxy)-2,5-difluorophenyl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)acetamide and (2,2-difluorocyclopropyl)methanol, and in the same manner as in Step A and Step B of Example 4, the title compound was obtained.

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

Procedure: Using N-((2S)-1-((2-(4-(benzyloxy)-2,5-difluorophenyl)[1,3]oxazolo[4,5-c]pyridin-6-yl)oxy)propan-2-yl)acetamide and (2,2-difluorocyclopropyl)methanol, and in the same manner as in Step A and Step B of Example 4, the title compound was obtained.

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

Procedure: Methanesulfonyl chloride (1.43 mL) was added to a solution of (2,2-difluorocyclopropyl)methanol (1.00 g) and triethylamine (2.58 mL) in THF (10 mL) dropwise at 0° C. The mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (1.47 g) as a colorless oil. the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over anhydrous magnesium sulfate concentrated in vacuo The residue was purified by silica gel column chromatography (hexane/ethyl acetate)