Ostarine(MK-2866) synthesis

Yield: 59.9%

Reaction Conditions:

with sodium carbonate in acetone for 3 h;Reflux;

Steps:

9
A mixture of bromoamide ((2R)-3- bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide, 50 g, 0.14 mol), anhydrous Na₂CO₃ (59.04 g, 0.43 mol), and 4-cyanophenol-<£* (25.44 g, 0.21 mol) in 500 mL of acetone was heated to reflux for 3 h and then concentrated under reduced pressure to give a solid. The resulting residue was treated with 500 mL of H₂O and then extracted with EtOAc (2 x 300 mL). The combined EtOAc extracts were washed with 10% NaOH (4 X 200 mL) and brine. The organic layer was dried over MgSO₄ and then concentrated under reduced pressure to give an oil which was treated with 300 mL of ethanol and an activated carbon. The reaction mixture was heated to reflux for 1 h and then the hot mixture was filtered through Celite. The filtrate was concentrated under reduced pressure to give an oil. This oil was purified by column chromatography using CH₂Cl₂/Et0Ac (80:20) to give an oil which was crystallized from CH₂Cl₂/hexane to give 33.2 g (59.9%) of deuterated (S)-_V-(4-cyano-3- (trifluoromethyl)phenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide as a colorless solid (a cotton type).[00571] ¹H NMR (CDC1₃/TMS) δ 1.63 (s, 3H, CH₃), 3.35 (s, 1H,OH), 4.07 (d, J = 9.04 Hz, IH, CH), 4.51 (d, J = 9.04 Hz, IH, CH), 6.97 - 6.99 (m, 2Η, ArH), 7.57-7.60 (m, 2Η, ArH), 7.81 (d, J = 8.55 Hz, IH, ArH), 7.97 (dd, J = 1.95, 8.55 Hz, IH, ArH), 8.12 (d, J = 1.95 Hz, IH, ArH), 9.13 (bs, 1Η, NH). Calculated Mass: 389.10, [M-H]^" 388.1. Mp: 92-94 ^°C.

References:

GTX, INC. WO2009/155481, 2009, A1 Location in patent:Page/Page column 123