反応 #2487443

反応方程式

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

溶媒

CH2Cl2

DMSO

反応条件

後処理

1. 1
   温度The reaction was cooled to rt
2. 2
   workup.ADDITIONpoured into a separatory funnel
3. 3
   洗浄The organic layer was washed
4. 4
   抽出the aqueous layer was back extracted twice with CH2Cl2
5. 5
   洗浄The combined organic layers were then washed three times with water
6. 6
   その他dried
7. 7
   その他Volatiles were removed by rotary evaporation
8. 8
   その他purified (ISCO, 12 g SiO2, 20-60% ethyl acetate to hexanes over 7 min followed by 7 min at 60%)

実験手順

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)−.

出典