2-(2-ethenoxyethoxy)ethanol

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

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

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

Procedure: Diethylene glycol (85 g, 0.8 mol), ethyl vinyl ether (80 ml, 0.8 mol) and, as the catalyst, mercuric acetate Hg(CH3COO)2 are charged to a 3-neck flask of 250 ml, equipped with condenser and inlets for the reactants and an inert gas. The system is kept under refluxing conditions, at a temperature of 70°-80° C., for 10 hours. The product is recovered by extraction with methylene chloride and is separated from the corresponding divinyl ether by distillation. In that way, 40 g (0.3 mol) of diethylene glycol monovinyl ether is obtained, with a yield of 40%, and is added to a solution containing 40 ml of ethyl ether and 53 ml of pyridine. To the resulting mixture, kept at room temperature and under a flowing nitrogen stream, methacryloyl chloride (38.3 g, 0.37 mol) is added dropwise. The addition of the chloride causes the immediate precipitation of pyridinium hydrochloride. The reaction is discontinued when the disappearance of the monovinyl ether is observed. The product (A) is recovered from the reaction mixture via HPLC, using silica as the stationary phase and a mixture of 8:1 hexane:ethylacetate as the eluent. 42 g of 99%-pure product is obtained, which corresponds to a yield of 70% relatively to diethylene glycol monovinyl ether. equipped with condenser and inlets for the reactants The product is recovered by extraction with methylene chloride is separated from the corresponding divinyl ether by distillation

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

Procedure: Diethylene glycol (85 g, 0.8 mol), ethyl vinyl ether (80 ml, 0.8 mol) and, as the catalyst, mercuric acetate Hg(CH3COO)2 are charged to a 3-neck flask of 250 ml, equipped with condenser and inlets for the reactants and an inert gas. The system is kept under refluxing conditions, at a temperature of 70°-80° C., for 10 hours. The product is recovered by extraction with methylene chloride and is separated from the corresponding divinyl ether by distillation. In that way, 40 g (0.3 mol) of diethylene glycol monovinyl ether is obtained, with a yield of 40%, and is added to a solution containing 40 ml of ethyl ether and 53 ml of pyridine. To the resulting mixture, kept at room temperature and under a flowing nitrogen stream, methacryloyl chloride (38.3 g, 0.37 mol) is added dropwise. The addition of the chloride causes the immediate precipitation of pyridinium hydrochloride. The reaction is discontinued when the disappearance of the monovinyl ether is observed. The product (A) is recovered from the reaction mixture via HPLC, using silica as the stationary phase and a mixture of 8:1 hexane:ethylacetate as the eluent. 42 g of 99%-pure product is obtained, which corresponds to a yield of 70% relatively to diethylene glycol monovinyl ether. equipped with condenser and inlets for the reactants The product is recovered by extraction with methylene chloride is separated from the corresponding divinyl ether by distillation

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

Procedure: In toluene (30 ml) was dissolved the 2-[(4-chlorophenyl)sulfonylmethyl]-1,4-difluorobenzene (520 mg, 1.72 mmol) obtained in Example 5. After addition of 2,2-(2-vinyloxyethoxy)ethanol (0.270 ml, 2.10 mmol) and cyanomethylenetri-n-butylphosphorane (500 mg, 2.07 mmol), the mixture was heated under reflux for 24 hours under an argon atmosphere. The reaction mixture was then allowed to cool down. After addition of 2-(2-vinyloxyethoxy)-ethanol (0.170 ml, 1.25 mmol) and cyanomethylenetri-n-butylphosphorane (300 mg, 1.24 mmol), the mixture was heated under reflux for 12 hours under an argon atmosphere. The reaction mixture was allowed to cool down and then concentrated under reduced pressure. The residue thus obtained was purified by silica gel chromatography (hexane:ethyl acetate=7:1) to yield a white solid. The resulting white solid was washed with hexane, whereby the title compound (140 mg, 20%) was obtained as a white powder. the mixture was heated under reflux for 24 hours under an argon atmosphere to cool down the mixture was heated under reflux for 12 hours under an argon atmosphere to cool down concentrated under reduced pressure The residue thus obtained was purified by silica gel chromatography (hexane:ethyl acetate=7:1) to yield a white solid The resulting white solid was washed with hexane, whereby the title compound (140 mg, 20%) was obtained as a white powder

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

Procedure: A solution of Example 87B (7.28 g, 20.72 mmol) in methyl cyclohexane (1.5 L) was degassed with nitrogen and (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium (250 mg, 0.294 mmol) was added. The mixture was stirred at room temperature overnight and diethyleneglycol vinyl ether (0.16 mL) was added to inactivate any remaining active catalyst. The mixture was stirred for 30 minutes, concentrated and purified by flash chromatography on silica using an Analogix system (0-10% ethyl acetate/heptane) to provide the title compound. MS (ESI+) m/z 346 (M+Na)+. was added The mixture was stirred for 30 minutes concentrated purified by flash chromatography on silica using an Analogix system (0-10% ethyl acetate/heptane)

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

Procedure: Diethylene glycol (85 g, 0.8 mol), ethyl vinyl ether (80 ml, 0.8 mol) and, as the catalyst, mercuric acetate Hg(CH3COO)2 are charged to a 3-neck flask of 250 ml, equipped with condenser and inlets for the reactants and an inert gas. The system is kept under refluxing conditions, at a temperature of 70°-80° C., for 10 hours. The product is recovered by extraction with methylene chloride and is separated from the corresponding divinyl ether by distillation. In that way, 40 g (0.3 mol) of diethylene glycol monovinyl ether is obtained, with a yield of 40%, and is added to a solution containing 40 ml of ethyl ether and 53 ml of pyridine. To the resulting mixture, kept at room temperature and under a flowing nitrogen stream, methacryloyl chloride (38.3 g, 0.37 mol) is added dropwise. The addition of the chloride causes the immediate precipitation of pyridinium hydrochloride. The reaction is discontinued when the disappearance of the monovinyl ether is observed. The product (A) is recovered from the reaction mixture via HPLC, using silica as the stationary phase and a mixture of 8:1 hexane:ethylacetate as the eluent. 42 g of 99%-pure product is obtained, which corresponds to a yield of 70% relatively to diethylene glycol monovinyl ether. equipped with condenser and inlets for the reactants The product is recovered by extraction with methylene chloride is separated from the corresponding divinyl ether by distillation

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-chloro-N-(3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (1.0 g, 2.2 mmol; prepared as in Example 65, step C)), 2-(2-(vinyloxy)ethoxy)ethanol (1.2 g, 8.8 mmol) and potassium hydroxide (0.61 g, 11 mmol) was dissolved in DMSO (10 mL). The reaction mixture was heated at 95° C. for 20 hours. The mixture was cooled to ambient temperature, transferred into water (100 mL) and saturated aqueous NaCl (200 mL) and stirred at ambient temperature for 4 hours. The resulting solid was collected by vacuum filtration and dried under vacuum to give the product (0.90 g). MS (ES+APCI) m/z=552.9 (M+H). The mixture was cooled to ambient temperature The resulting solid was collected by vacuum filtration dried under vacuum

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

Procedure: In toluene (30 ml) was dissolved the 2-[(4-chlorophenyl)sulfonylmethyl]-1,4-difluorobenzene (520 mg, 1.72 mmol) obtained in Example 5. After addition of 2,2-(2-vinyloxyethoxy)ethanol (0.270 ml, 2.10 mmol) and cyanomethylenetri-n-butylphosphorane (500 mg, 2.07 mmol), the mixture was heated under reflux for 24 hours under an argon atmosphere. The reaction mixture was then allowed to cool down. After addition of 2-(2-vinyloxyethoxy)-ethanol (0.170 ml, 1.25 mmol) and cyanomethylenetri-n-butylphosphorane (300 mg, 1.24 mmol), the mixture was heated under reflux for 12 hours under an argon atmosphere. The reaction mixture was allowed to cool down and then concentrated under reduced pressure. The residue thus obtained was purified by silica gel chromatography (hexane:ethyl acetate=7:1) to yield a white solid. The resulting white solid was washed with hexane, whereby the title compound (140 mg, 20%) was obtained as a white powder. the mixture was heated under reflux for 24 hours under an argon atmosphere to cool down the mixture was heated under reflux for 12 hours under an argon atmosphere to cool down concentrated under reduced pressure The residue thus obtained was purified by silica gel chromatography (hexane:ethyl acetate=7:1) to yield a white solid The resulting white solid was washed with hexane, whereby the title compound (140 mg, 20%) was obtained as a white powder

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

Procedure: A solution of Example 87B (7.28 g, 20.72 mmol) in methyl cyclohexane (1.5 L) was degassed with nitrogen and (1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium (250 mg, 0.294 mmol) was added. The mixture was stirred at room temperature overnight and diethyleneglycol vinyl ether (0.16 mL) was added to inactivate any remaining active catalyst. The mixture was stirred for 30 minutes, concentrated and purified by flash chromatography on silica using an Analogix system (0-10% ethyl acetate/heptane) to provide the title compound. MS (ESI+) m/z 346 (M+Na)+. was added The mixture was stirred for 30 minutes concentrated purified by flash chromatography on silica using an Analogix system (0-10% ethyl acetate/heptane)

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

Procedure: Diethylene glycol (85 g, 0.8 mol), ethyl vinyl ether (80 ml, 0.8 mol) and, as the catalyst, mercuric acetate Hg(CH3COO)2 are charged to a 3-neck flask of 250 ml, equipped with condenser and inlets for the reactants and an inert gas. The system is kept under refluxing conditions, at a temperature of 70°-80° C., for 10 hours. The product is recovered by extraction with methylene chloride and is separated from the corresponding divinyl ether by distillation. In that way, 40 g (0.3 mol) of diethylene glycol monovinyl ether is obtained, with a yield of 40%, and is added to a solution containing 40 ml of ethyl ether and 53 ml of pyridine. To the resulting mixture, kept at room temperature and under a flowing nitrogen stream, methacryloyl chloride (38.3 g, 0.37 mol) is added dropwise. The addition of the chloride causes the immediate precipitation of pyridinium hydrochloride. The reaction is discontinued when the disappearance of the monovinyl ether is observed. The product (A) is recovered from the reaction mixture via HPLC, using silica as the stationary phase and a mixture of 8:1 hexane:ethylacetate as the eluent. 42 g of 99%-pure product is obtained, which corresponds to a yield of 70% relatively to diethylene glycol monovinyl ether. equipped with condenser and inlets for the reactants The product is recovered by extraction with methylene chloride is separated from the corresponding divinyl ether by distillation