Toluene → Ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-4-formyl-3-methylnaphthalen-2-yl)acetate

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl 2-(4-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate (75 mg, 0.153 mmol), K2CO3 (317 mg, 2.29 mmol), PdCl2(dppf) (11.2 mg, 15.3 μmol), and potassium vinyltrifluoroborate (103 mg, 0.766 mmol) in H2O (500 μL), EtOH (absolute, 500 μL), and PhMe (1.0 mL) was heated to 100° C. for 4 h in a sealed vessel. The reaction was cooled to 23° C., diluted with H2O (30 mL), and extracted with EtOAc (3×). Combined organic phases were dried (Na2SO4), filtered, concentrated, and evaporated from MeOH in vacuo (2×). The residue was treated with MeOH (3.0 mL), and DCM (3.0 mL), and cooled to −78° C. The solution was sparged with ozone in O2 for 5 min. After min past the end of the sparge, the reaction was treated with DMS (100 μL) and warmed to 0° C. 10% Na2S2O3 (2.0 mL) was added, and the reaction was stirred at 23° C. for several minutes. The reaction was diluted with H2O and DCM, then filtered over Celite. The filtrate was extracted with DCM (2×). Organic phases were combined, dried (Na2SO4), filtered, and concentrated. DCM was added, and the solution was wet-loaded onto a 12 g “gold” ISCO silica gel column and purified by flash chromatography (ethyl acetate/hexanes 3:97 isocratic) giving the desired product (34 mg, 51% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.01 (s, 1H), 8.73 (d, J=8.2 Hz, 1H), 7.56-7.22 (m, 7H), 5.16 (s, 1H), 4.24-4.12 (m, 2H), 2.81 (s, 3H), 1.23 (t, J=7.0 Hz, 3H), 1.00 (s, 9H).

Provenance & Evidence