Potassium tert-butoxide → N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-(spiro[3.5]nonan-7-ylmethoxy)benzamide

To a solution of spiro[3.5]nonan-7-ylmethanol (0.58 g, 3.76 mmol) in anhydrous dimethyl sulfoxide (20 mL) was added potassium t-butoxide (1.05 g, 9.35 mmol) at ambient temperature. After stirring at ambient temperature for 30 minutes, N-(azetidin-1-ylsulfonyl)-5-chloro-2,4-difluorobenzamide (1.17 g, 3.76 mmol) was added to the reaction mixture; stirring was continued at ambient temperature for 2 hours. The mixture was cooled to 0° C. and quenched with 5% aqueous hydrochloride acid (10 mL) followed by extraction with ethyl acetate (100 mL). The organic layer was washed with water (2×40 mL) and brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo, the crude product was purified by silica gel column chromatography using 10-40% ethyl acetate (containing 0.2% acetic acid) in hexanes to afford the title compound as a colorless solid (0.60 g, 36%): 1H NMR (300 MHz, CDCl3) δ 8.60 (d, J=15.6 Hz, 1H), 8.10 (d, J=8.4 Hz, 1H), 6.66 (d, J=13.8 Hz, 1H), 4.23 (t, J=7.8 Hz, 4H), 3.82 (d, J=6.3 Hz, 2H), 2.32-2.20 (m, 2H), 1.88-1.66 (m, 11H), 1.35-1.24 (m, 2H), 1.18-1.05 (m, 2H); MS (ES+) m/z 445.1, 447.1 (M+1), MS (ES−) m/z 443.2, 445.2 (M−1).

1. stirringstirring
2. waitwas continued at ambient temperature for 2 hours
3. temperatureThe mixture was cooled to 0° C.
4. customquenched with 5% aqueous hydrochloride acid (10 mL)
5. extractionfollowed by extraction with ethyl acetate (100 mL)
6. washThe organic layer was washed with water (2×40 mL) and brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationThe filtrate was concentrated in vacuo
10. customthe crude product was purified by silica gel column chromatography

ORD 기록

ord-c261f7b35d9e44c6b5a0c65822381d0c

출처 데이터셋

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08952169B2