Oxygen → (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(6-methoxypyridin-3-yl)piperidin-3-yl)-6-phenyl-1,3-oxazinan-2-one

Participants

Reaction Conditions

Reaction Steps

A suspension of 6-methoxypyridin-3-ylboronic acid (4 mg, 1.5equiv), Cu(OAc)2 (1 mg, cat. amount), potassium fluoride (1.1 mg, 1.05 equiv), and powdered activated 4 Å Molecular Sieves (15 mg) in acetonitrile (1.5 mL) was stirred in a test tube at ambient conditions for 10 min. A solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-piperidin-3-yl)-1,3-oxazinan-2-one TFA salt (6 mg, 0.018 mmol) in acetonitrile (1 mL) was added. The test tube was sealed with a septum and a balloon of oxygen gas was attached to maintain the oxygen atmosphere. The mixture was heated overnight at 85° C. LC-MS found the product peak. The mixture was filtered and purified by prep HPLC to afford (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(6-methoxypyridin-3-yl)piperidin-3-yl)-6-phenyl-1,3-oxazinan-2-one (4.5 mg, 76% yield). LC-MS Method 1 tR=1.37 min, m/z=440(M+1); 1H NMR (CD3OD) 7.82(m, 2H), 7.43-7.29(m, 5H), 7.11(m, 1H), 4.14(m, 1H), 4.00(s, 3H), 3.56(t, 1H), 2.77(m, 3H), 2.52(m, 2H), 2.19(s, 2H), 1.23(s, 3H), 0.95(s, 3H).

Provenance & Evidence