SC-1 synthesis

Yield:1313019-65-6 80%

Reaction Conditions:

Stage #1: bis(trichloromethyl) carbonate;4-chloro-3-trifluoromethyl-anilinewith triethylamine in tetrahydrofuran at 50; for 0.5 h;
Stage #2: 4-amino-4'-cyanodiphenyl ether in tetrahydrofuran at 50; for 0.5 h;

Steps:

6.2.1. Procedures for compound 1

To a 50 mL THF solution of triphosgen (0.30 g, 1.0 mmol), 4-chloro-3-(trifluoromethyl)aniline (0.21g, 1.1mmol) and 2 equivalent of triethyl amine were added. The mixture was heated to 50 °C for 30 min. After the temperature was back to room temperature, 4-(4-aminophenoxy)benzonitrile in the 10 mL THF solution was added to the mixture and heated to 50 °C for another 30 min. The mixture was evaporated, diluted with water and extracted with EtOAc. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 1 (0.34 g, 80%).

References:

Chen, Kuen-Feng;Tai, Wei-Tien;Huang, Jui-Wen;Hsu, Cheng-Yi;Chen, Wei-Lin;Cheng, Ann-Lii;Chen, Pei-Jer;Shiau, Chung-Wai [European Journal of Medicinal Chemistry,2011,vol. 46,# 7,p. 2845 - 2851] Location in patent:experimental part