7-[(5-Methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane dihydrochloride (2-1b, 1.8 g, 5.2 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indan-1-one (SM-1a, 2.0 g, 7.75 mmol) were dissolved in anhydrous dichloroethane (50 mL). Triethylamine (2.88 mL, 20.6 mmol) was added to the solution followed by titanium(IV) isopropoxide (3.06 mL, 2.09 g) and the reaction mixture was stirred at ambient temperature for 1 hour. Sodium triacetoxyborohydride (4.38 g, 20.7 mmol) was added and the reaction was stirred at room temperature for 15 hours. The reaction was quenched by the addition of 20 mL saturated sodium bicarbonate. The aqueous solution was washed with 100 mL of dichloromethane and the organic solution was washed with brine and dried over anhydrous Na2SO4. Removal of the solvent under vacuum afforded the crude product (4.0 g) as a brown foam. The crude product was purified by silica chromatography on an Analogix system (Analogix Inc., Burlington, Wis.), eluting with 1-10% MeOH in CH2Cl2 to give the title compound (2-1c) as a brown paste (1.1 g, 41%). MS (ES+) 518.6 (M+H)+. 1H NMR (CDCl3) δ1.27 (s, 12H), 1.50-1.65 (m, 4H), 1.76-1.85 (m, 1H), 1.99-2.10 (m, 1H), 2.64-2.76 (m, 1H), 2.90-2.98 (m, 1H), 3.00-3.13 (m, 4H), 3.42 (d, 4H), 3.77 (s, 3H), 3.80 (s, 2H), 3.85 (s, 1H), 7.08-7.12 (m, 1H), 7.18-7.22 (m, 2H), 7.54-7.58 (m, 1H), 7.63 (s, 1H), 8.14-8.16 (m, 1H).
