Acetaldehyde → 4-(adamantan-1-ylmethoxy)-2-fluoro-N-((2-hydroxypropyl)sulfonyl)-benzamide

Temperature

-78 °C

To a solution of 4-(adamantan-1-ylmethoxy)-5-bromo-2-fluoro-N-(methylsulfonyl)benzamide (0.340 g, 0.74 mmol) in anhydrous tetrahydrofuran (5 mL) was added tert-butyllithium (1.7 M solution in pentane, 1.31 mL, 2.22 mmol) at −78° C. The reaction mixture was stirred for 30 minutes at −78° C. followed by addition of acetaldehyde (0.21 mL, 3.70 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 16 hours. After quenched with 1 N hydrochloric acid (5 mL), the mixture was diluted with ethyl acetate (100 mL). The organic phase was washed with brine (5 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate gave a residue which was purified by reverse-phase preparative HPLC to afford the title compound as an off-white solid (0.075 g, 24%): 1H NMR (300 MHz, DMSO-d6) δ 11.79 (s, 1H), 7.60 (t, J=8.7 Hz, 1H), 6.93 (dd, J=13.0, 2.2 Hz, 1H), 6.86 (dd, J=8.7, 2.3 Hz, 1H), 5.04 (br s, 1H), 4.17-4.07 (m, 1H), 3.65-3.56 (m, 1H), 3.63 (s, 2H), 3.45 (dd, J=14.3, 5.1 Hz, 1H), 2.02-1.94 (m, 3H), 1.76-1.57 (m, 12H), 1.20 (d, J=6.3 Hz, 3H); MS (ES−) m/z 424.2 (M−1).

1. temperatureto warm to ambient temperature
2. stirringstirred for 16 hours
3. customAfter quenched with 1 N hydrochloric acid (5 mL)
4. additionthe mixture was diluted with ethyl acetate (100 mL)
5. washThe organic phase was washed with brine (5 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. customConcentration of the filtrate gave a residue which
9. customwas purified by reverse-phase preparative HPLC

ORD record

ord-6fa39a0c71274920886a15360518f593

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2