To a solution of 2-(4-bromo-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide (110 mg, 0.25 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (63 mg, 0.25 mmol), and potassium acetate (49 mg, 0.5 mmol) in 1,4-dioxane (2.5 mL) was added PdCl2(dppf)-CH2Cl2 adduct (20.4 mg, 0.025 mmol). The reaction mixture was purged with nitrogen and then was heated at 120° C. for 4 h. The reaction mixture was cooled and 7-bromo-3-fluoroquinoline (56.5 mg, 0.25 mmol) and 2M aq K2CO3 (0.27 mL, 0.55 mmol) were added. The reaction mixture was purged with nitrogen and was heated with stirring at 100° C. for one hour. The reaction mixture was diluted with dichloromethane (60 mL), and salts were filtered away. The organic mixture was filtered through a plug of celite and sodium sulfate. The filtrate was treated with a small amount of Silicycle Si-thiol resin for 30 min and was then filtered and concentrated in vacuo. Purification of the residue by reverse phase HPLC (10-70% acetonitrile:water with 0.1% NH4OH) followed by chiral HPLC (Chromegachiral CC4, methanol) afforded the title product in >98% ee (34 mg, 27%). αD=+37 deg (c=0.04, methanol); MS(ES)+ m/e 507 [M+H]+; 1H NMR (400 MHz, CD2Cl2) δ ppm 0.60-0.69 (m, 2 H) 0.77-0.86 (m, 2 H) 1.64-1.77 (m, 2 H) 1.85-1.97 (m, 2 H) 2.26-2.38 (m, 1 H) 2.57 (d, J=14.40 Hz, 1 H) 2.66-2.76 (m, 2 H) 2.79 (d, J=10.86 Hz, 1 H) 3.15 (s, 2 H) 4.00 (d, J=1.77 Hz, 2 H) 4.53 (s, 1 H) 5.63 (br. s., 1 H) 7.26 (d, J=3.79 Hz, 1 H) 7.46 (t, J=7.71 Hz, 1 H) 7.56 (d, J=1.77 Hz, 1 H) 7.62 (dd, J=7.96, 1.89 Hz, 1 H) 7.84-7.93 (m, 2 H) 7.93-8.00 (m, 1 H) 8.38 (s, 1 H) 8.88 (d, J=2.78 Hz, 1 H).
