Hydrochloric Acid → {4-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]phenyl}boronic acid

Temperature

-78 °C

n-Butyllithium (2.5M in hexanes, 0.56 mL, 1.4 mmol) was added dropwise to a solution of 4-{[(4-bromophenyl)oxy]methyl}-1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]piperidine (prepared as in Example 24, Step 1, 380 mg, 1 mmol) in THF (5 mL) at −78° C. The mixture was stirred at −78° C. for 2 h, and was then charged with a cooled solution (−78° C.) of triisopropylborate (0.46 mL, 2 mmol) in THF (3 mL) at −78° C. The reaction mixture was allowed to warm up to ambient temperature and stirred at ambient temperature overnight. The reaction mixture was charged with 1N HCl (20 mL) and stirred at ambient temperature for 1 h. The mixture was then extracted with Et2O, and the organic extracts were dried over MgSO4, filtered, and the filtrate was concentrated. The crude product was purified by chromatography on a silica gel column using 0 to 7% MeOH/CH2Cl2 to give 120 mg (35%) of the {4-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]phenyl}boronic acid as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.82 (s, 2H), 7.69 (d, 2H, J=8.8 Hz), 6.86 (d, 2H, J=8.8 Hz), 4.04-3.92 (m, 2H), 3.85 (d, 2H, J=6.4 Hz), 3.15-3.05 (m, 2H), 2.84-2.73 (m, 1H), 2.04-1.94 (m, 1H), 1.88-1.78 (m, 2H), 1.37-1.22 (m, 2H), 1.16 (d, 6H, J=6.9 Hz); LRMS (ESI), m/z 346 (M+H).

1. temperatureto warm up to ambient temperature
2. stirringstirred at ambient temperature overnight
3. stirringstirred at ambient temperature for 1 h
4. extractionThe mixture was then extracted with Et2O
5. dry with materialthe organic extracts were dried over MgSO4
6. filtrationfiltered
7. concentrationthe filtrate was concentrated
8. customThe crude product was purified by chromatography on a silica gel column

ORD record

ord-dadef7ed87f74b2883ab30998ffbb742

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101634B2