Reacción #157898

Ecuación de reacción

2,4-Difluorophenol

tributylphosphine

{5-cyclopropyl-6-[(4-methoxybenzyl)oxy]pyridin-2-yl}[4-(cyclopropylsulfonyl)phenyl]methanol

potassium carbonate

→

3-cyclopropyl-6-{[4-(cyclopropylsulfonyl)phenyl](2,4-difluorophenoxy)methyl}-2-[(4-methoxybenzyl)oxy]pyridine

Rendimiento 77.1%

Disolventes

tetrahydrofuran

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroreturned to room temperature
2. 2
   workup.STIRRINGstirred overnight
3. 3
   Extracciónfollowed by extraction with chloroform
4. 4
   SecadoThe organic layer was dried over anhydrous magnesium sulfate
5. 5
   Filtraciónfiltered
6. 6
   ConcentraciónThe filtrate was concentrated under reduced pressure
7. 7
   OtroThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=92:8→34:66)

Procedimiento

2,4-Difluorophenol (219 mg), tributylphosphine (340 mg) and N,N,N′,N′-tetramethylazodicarboxyamide (289 mg) were sequentially added to a solution of {5-cyclopropyl-6-[(4-methoxybenzyl)oxy]pyridin-2-yl}[4-(cyclopropylsulfonyl)phenyl]methanol (390 mg) in tetrahydrofuran (12 mL). After replacement with nitrogen, the mixture was stirred under reflux at an external temperature of 86° C. for six hours, returned to room temperature and stirred overnight. The reaction solution was poured into water and a potassium carbonate solution was added, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=92:8→34:66) to give 3-cyclopropyl-6-{[4-(cyclopropylsulfonyl)phenyl](2,4-difluorophenoxy)methyl}-2-[(4-methoxybenzyl)oxy]pyridine as a yellow gum (373 mg, 77%).

Fuente