p-Toluenesulfonic acid → 5'-{[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonyl}spiro[1,3-dioxane-2,3'-indol]-2'(1'H)-one

To a rapidly and efficiently stirred suspension of 5-{[(2S)-2-(phenoxymethyl)pyrrolidin-1-yl]sulfonyl}-1H-indole-2,3-dione (16.13 g, 41.7 mmol) in benzene (785 mL) was added p-toluenesulfonic acid mono-hydrate (1.58 g, 8.34 mmol, 0.2 mole % ) and 1,3 propanediol (12.2 mL, 167 mmol, 4 eq) and the mixture was heated to reflux under a Dean Stark Trap for 5 hr. Additional p-toluenesulfonic acid (1.50 g, 0.2 mole % ) was added and the mixture was heated for another 1.5 hr. After cooling in an ice bath, the black reaction mixture was washed with sat. aq. NaHCO3 (3×350 mL), water (2×500 mL), brine (3×500 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified on silica gel eluting with CH2Cl2 followed by 50/50 Pet ether/EtOAc to give the title compound as an orange solid (11.44 g, 61.7% yield). NMR (400 MHz, DMSO-d6): consistent. MS: (ES−) m/z 443 [M−H]. MS: (ES+) m/z 445 [M+H].

1. temperaturethe mixture was heated
2. temperatureto reflux under a Dean Stark Trap for 5 hr
3. temperaturethe mixture was heated for another 1.5 hr
4. temperatureAfter cooling in an ice bath
5. washthe black reaction mixture was washed with sat. aq. NaHCO3 (3×350 mL), water (2×500 mL), brine (3×500 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified on silica gel eluting with CH2Cl2

ORDレコード

ord-c2b30cff8b954c1d954827f98ab444cf

出典データセット

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07256198B2