反应详情

温度

59 °C

A suspension of 5′-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl}spiro[1,3-dioxane-2,3′-indol]-2′(1′H)-one (6.8 g, 17.8 mmol) and benzyltrimethyl-ammonium hydroxide (40% by weight aqueous solution, 1.94 mL, 4.27 mmol, 0.25 eq) in absolute EtOH (80 mL) was heated to 59° C. and acryonitrile (2.93 mL, 44.5 mmol, 2.5 eq) was added drop-wise. After heating 5 hrs at 72° C. the reaction was cooled to room temperature, poured into H2O (160 mL) and extracted with EtOAc (3×150 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was flash chromatographed (Biotage KP silica gel, 99/1 then 98/2 CH2Cl2/CH3OH) to give the title compound as a white solid (4.5 g, 58% yield). Anal: Calc'd for C20H25N3O6S: C, 55.16; H, 5.79; N, 9.65; Found: C, 55.06, H, 5.94, N, 9.52; NMR (400 MHz, DMSO-d6): consistent. MS: (ES+) m/z 436[M+H] m.p.: 138-141° C.

1. additionwas added drop-wise
2. temperatureAfter heating 5 hrs at 72° C. the reaction
3. temperaturewas cooled to room temperature
4. extractionextracted with EtOAc (3×150 mL)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customchromatographed (Biotage KP silica gel, 99/1