Reacción #2487443

Ecuación de reacción

5-(2,2-difluoro-2-phenylethoxy)-2-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridine

1H-tetrazole

K2CO3

N2

NH4Cl

→

title compound 119

1-(5-(2,2-difluoro-2-phenylethoxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol

Disolventes

CH2Cl2

DMSO

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction was cooled to rt
2. 2
   workup.ADDITIONpoured into a separatory funnel
3. 3
   LavadoThe organic layer was washed
4. 4
   Extracciónthe aqueous layer was back extracted twice with CH2Cl2
5. 5
   LavadoThe combined organic layers were then washed three times with water
6. 6
   Otrodried
7. 7
   OtroVolatiles were removed by rotary evaporation
8. 8
   Otropurified (ISCO, 12 g SiO2, 20-60% ethyl acetate to hexanes over 7 min followed by 7 min at 60%)

Procedimiento

To a magnetically stirred mixture of 5-(2,2-difluoro-2-phenylethoxy)-2-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridine (81 mg, 0.184 mmol, compound X), and 1H-tetrazole (19.37 mg, 0.277 mmol) in dry DMSO (1229 μl) was added K2CO3 (28.0 mg, 0.203 mmol) in a 20 mL vial under N2 atmosphere. The reaction mixture was stirred at 60° C. overnight. The reaction was cooled to rt, diluted with CH2Cl2 and poured into a separatory funnel containing sat. aq. NH4Cl. The organic layer was washed and then the aqueous layer was back extracted twice with CH2Cl2. The combined organic layers were then washed three times with water and dried by passing through a phase separator. Volatiles were removed by rotary evaporation and the resulting residue was loaded onto a pad of SiO2 and purified (ISCO, 12 g SiO2, 20-60% ethyl acetate to hexanes over 7 min followed by 7 min at 60%) to afford the title compound 119. Yield=56 mg (59.6%) of a light yellow viscous oil. 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 8.21 (d, J=2.8 Hz, 1H), 7.57-7.45 (m, 6H), 7.41 (s, 1H), 7.33-7.24 (m, 2H), 6.80-6.70 (m, 1H), 6.70-6.62 (m, 1H), 5.58 (d, J=14.3 Hz, 1H), 5.07 (d, J=15.1 Hz, 1H), 4.42 (t, J=11.9 Hz, 2H). 1H decoupled-19F NMR (376 MHz, CDCl3) δ −102.97 (dd, J=261.4, 15.2 Hz, 1F), −103.88 (ddd, J=43.5, 14.9, 9.8 Hz, 1F), −104.07 (s, 2F), −108.15 (d, J=9.7 Hz, 1F), −110.87 (dd, J=261.4, 43.2 Hz, 1F). MS(ESI): m/z calcd for C23H17F6N5O2: 509.404; found: 510.2 (M+H)+, 508.6 (M−H)−.

Fuente