Cyclopropylacetylene → HCID 54068872, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred, cooled (0° C.) solution of 2.0 mL (7.0 mmol) of 3.5M cyclopropylacetylene in toluene was added 2 mL of THF followed by 2.8 mL (7.0 mmol) of 2.5M n-BuLi in hexanes over 2 min. The solution was stirred 5 min. at 0° C., warmed to RT, and stirred a further 20 min. The reaction was cooled to 0° C. and treated with a solution of 300 mg (1.24 mmol) of 2'-amino-5'-chloro-3'-fluoro-2,2,2-trifluoroacetophenone in 3mL of THF over 2 min. The solution was stirred an additional 10 min. and the cold bath was removed. The reaction was stirred 5 min and poured into 0.5N citric acid. The mixture was extracted with ether, and the organic extract was washed with water then brine, dried (MgSO4), and concentrated under reduced pressure. Chromatography on silica gel (elution with hexanes then 3:1 hexanes-ether) afforded 185 mg (49%) of (±)-2-amino-5-chloro-3-fluoro-α-(cyclopropylethynyl)-α-(trifluoromethyl)benzyl alcohol as an off-white solid, mp 131°-135° C. 1H NMR (300 MHz, CDCl3) δ7.34-7.36(m, 1H); 7.04(dd, 1H, J=10.4, 2.4 Hz); 4.58(br. s, 2H); 3.82(br. s, 1H); 1.35-1.44(m, 1H); 0.80-0.99(m, 4H). 19F NMR (282 MHz, CDCl3) δ-131.5(s, 1F), -80.5(s, 3F). High resolution mass spec: calculated for C13H11NOClF4 (M+H)+ : 308.0470, found: 308.0465.

Provenance & Evidence