反应详情

Magnesium (3.65 g, 150 mmol) and an iodine crystal were provided in a nitrogen atmosphere and heated. Abs. ether (10 mL) was then added and a solution of 4-bromoanisole (18.8 mL, 150 mmol) in abs. ether (150 mL) was added in drops so that the ether lightly boiled. The solution formed was subsequently stirred for 1 h at RT and then mixed in drops with a solution of 8-dimethylamino-1,4-dioxa-spiro[4.5]decane-8-carbonitrile (10.5 g, 50.0 mmol) in abs. THF (100 mL), and the solution heated to 37-40° C. until boiling during the addition. A precipitate separated out and the batch was stirred overnight at RT. The solution was mixed with NH4Cl solution with ice cooling, the phases were separated, the aqueous phase extracted three times with ether, the combined organic phases washed with saturated NaCl solution and water, dried over Na2SO4 and concentrated to low volume in a vacuum. Flash chromatography of the residue with ethyl acetate/methanol (20:1→9:1→4:1→1:4→MeOH) gave the desired product.

1. temperatureheated
2. customThe solution formed
3. additionuntil boiling during the addition
4. customA precipitate separated out
5. stirringthe batch was stirred overnight at RT
6. additionThe solution was mixed with NH4Cl solution with ice cooling
7. customthe phases were separated
8. extractionthe aqueous phase extracted three times with ether
9. washthe combined organic phases washed with saturated NaCl solution and water
10. dry with materialdried over Na2SO4
11. concentrationconcentrated to low volume in a vacuum