反应详情

温度

-50 °C

A flame dried flask was charged with DCM (20 ml) and oxalyl chloride (0.90 g, 0.62 mmol) under N2. The vessel was cooled to −50° C. in an acetorntrile:dry ice bath. DMSO (1.1 g, 14.2 mmol) was added drop wise after which the solution was stirred for 2 minutes. A solution of 2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol from step 6 of Example 1 (1 g, 3.55 mmol) in DCM (15 ml) was added drop wise and the mixture was stirred for 15 minutes. TEA (2.88 g, 28.4 mmol) was added, the mixture stirred for 15 minutes at −50° C. and then allowed to warm to RT for 1 hour. Water (15 ml) was then added drop wise, the mixture diluted with an additional 50 ml water. The mixture was then place in a separatory funnel, shaken and the layers separated. The aqueous phase was extracted with DCM (2×35 ml), the organic fractions combined, washed with brine, dried over Na2SO4, filtered, and the volatiles removed in vacuum strip. The product was purified by chromatography on SiO2 eluting with 30% acetone:hexanes. LRMS calc: 279.11; obs: 280.05 (M+1).

1. customA flame dried flask
2. stirringthe mixture was stirred for 15 minutes
3. stirringthe mixture stirred for 15 minutes at −50° C.
4. temperatureto warm to RT for 1 hour
5. stirringplace in a separatory funnel, shaken
6. customthe layers separated
7. extractionThe aqueous phase was extracted with DCM (2×35 ml)
8. washwashed with brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customthe volatiles removed in vacuum strip
12. customThe product was purified by chromatography on SiO2 eluting with 30% acetone