Org Prep Daily

October 13, 2006

Spirochromanones

Filed under: procedures — milkshake @ 1:07 am

spiro1.gif

Pyrrolidine 0.25mL (3.0mmol) was added to a mixture of 2-hydroxy-5-chloroacetophenone 6.176g (36.2mmol) and 1-acetyl-4-piperidone 5.113g (36.2mmol)  in methanol 12mL. The mixture was heated under reflux (Ar, oil bath 80C) for 11 hours. The reaction mixture was diluted with ether 80mL and allowed to crystallize at RT for 1 hour. The precipitated product was collected by filtration, washed with ether (2x20mL) and dried on highvac. Y=8.286g (78%) of a white crystalline solid.

1H(d6-DMSO, 400MHz): 7.658(m, 2H), 7.151(d, 8.7Hz, 1H), 4.084(app br d, 10.0Hz, 1H), 3.632(app br d, 13.9Hz, 1H), 3.360(m, 1H), 2.966(td, t:12.5Hz, d:3.0Hz, 1H), 2.876(s, 2H), 2.003(s, 3H), 1.900(app br t, 16.0Hz, 2H), 1.721(m, 1H), 1.569(m, 1H)

spiro2.gif 

The same procedure and scale, Y=8.487g (76%) of a white crystalline solid 1H(d6-DMSO, 400MHz): 7.641(s, 1H), 7.149 (s, 1H), 4.089(app br d, 13.3Hz, 1H), 3.630(app br d, 13.9Hz, 1H), 3.347(m, 1H), 2.948(td, t:12.5Hz, d:2.8Hz, 1H), 2.833(s, 2H), 2.341(s, 3H), 2.002(s, 3H), 1.894(app br t, 16.0Hz, 2H), 1.716(m, 1H), 1.564(m, 1H)  

 spiro3.gif 

Pyrrolidine 0.455mL with 2-hydroxy-5-fluoroacetophenone 10.110g (65.59mmol) and 1-acetyl-4-piperidone 5.113g (65.59mmol)  in methanol 22mL was heated under reflux (Ar, oil bath 80C) for 10 hours. The reaction mixture was diluted with ether 150mL and allowed to crystallize at RT for 8 hours. The precipitated pure product (11.176g) was collected by filtration, washed with ether (4x20mL) and dried on highvac. Cooling the supernatants to 5C (fridge, over weekend), additional product 3.930g precipitated. This second crop was re-crystallized from a mixture benzene-cyclohexane 1:2 to provide 3.761g of a pure product. Combined Y=14.937g (82%) of a light tan crystalline solid

1H(d6-DMSO, 400Mz): 7.494(td,t:8.4Hz,d:3.2Hz,1H), 7.436(dd,8.4Hz,3.2Hz, 1H), 7.160(dd,9.0Hz.4.3Hz,1H), 4.090(br m, 1H), 3.638(br m, 1H), 3.370(m, 1H), 2.976(m, 1H)2.870(s, 2H), 2.009(s, 3H), 1.906(app br t, 2H), 1.726(m, 1H), 1.575(m, 1H); 19F(d6-DMSO, 376.5MHz): -121.92 (m, 1F)

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