Ethanol → 2-Tert-butoxy-2-(1-(4-chlorophenyl)-4-(3-(dimethylamino)prop-1-ynyl)-3-methylnaphthalen-2-yl)acetic acid

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl 2-(4-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate (40 mg, 81.7 μmol), N,N-dimethylpropargylamine (26 μL, 0.245 mmol), PdCl2(PPh3)2 (5.7 mg, 16.3 μmol), CuI (3.1 mg, 16.3 μmol) and THF (1.00 mL) was heated to 70° C. for 18 h in a sealed vessel. Conversion was incomplete, so the vessel was charged with more PdCl2(PPh3)2 (5.7 mg, 16.3 μmol) and CuI (3.1 mg, 16.3 μmol) and heated to 100° C. for an additional 26 h. The reaction was cooled to 23° C. THF (1.0 mL), EtOH (absolute, 500 μL), and H2O (500 μL) were added followed by LiOH monohydrate (100 mg, 2.37 mmol). The reaction was heated to 100° C. for 4 h. After cooling to 23° C., the crude reaction was filtered through a 0.45 micron filter, and directly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). The product-containing fractions were combined and lyophilized, giving the title compound (mono trifluoroacetic acid salt) (6.8 mg, 15%). 1H NMR (400 MHz, DMSO-d6) δ 12.92 (s, broad, 1H), 10.26 (s, broad, 1H), 8.30 (d, J=8.6 Hz, 1H), 7.71-7.62 (m, 3H), 7.47-7.43 (m, 2H), 7.34 (d, J=8.2 Hz, 1H), 7.22 (d, J=8.6 Hz, 1H), 5.03 (s, 1H), 4.56 (s, 2H), 2.96 (s, 6H), 2.72 (s, 3H), 0.90 (s, 9H). 19F NMR (377 MHz, DMSO-d6) δ−74.1 (s) LCMS-ESI+ (m/z): [M+H]+ calcd for C28H31ClNO3: 464.2; Found: 464.0.

Provenance & Evidence