Acetaldehyde → HCID 68723789, compound

Temperature

-10 °C

At −78° C. under N2, a solution of diisopropylamine (0.53 ml, 3.72 mmol) in anhydrous THF (2.75 ml) was treated dropwise with a solution of 1.6M n-BuLi in hexane (2.33 ml, 2.75 mmol). The resulting solution was warmed to −10° C., cooled to −78° C., and treated dropwise with a solution of 1-(5-methylspiro[2.5]oct-5-en-4-yl)ethanone (470 mg, 2.87 mmol) in anhydrous THF (2.75 ml). The resulting solution was warmed to −20° C., cooled to −78° C. and treated with a solution of acetaldehyde (0.81 ml, 14.3 mmol) in anhydrous THF (2.75 ml). The resulting solution was warmed to −10° C., cooled to −78° C., and treated slowly with a mixture of 2N HCl (6 ml) and of a saturated aqueous solution of NaCl (3.6 ml). The mixture was then warmed to 0° C., the aqueous phase extracted three times with Et2O and the combined organic phases washed with a saturated aqueous solution of NaHCO3, a saturated aqueous solution of NH4Cl, a saturated aqueous solution of NaCl, dried (Na2SO4), and concentrated. The residue (596 mg) was dissolved in toluene (20 ml) and treated with para-toluene sulfonic acid monohydrate (27 mg, 0.143 mmol). The resulting solution was stirred at 80° C. for 3 h, cooled, and poured into a saturated aqueous solution of NaHCO3. The aqueous phase was extracted three times with Et2O and the combined organic phases washed with a saturated aqueous solution of NH4Cl, a saturated aqueous solution of NaCl, and concentrated. FC (200 g SiO2, hexane/Et2O 10:0.5) of the crude product (730 mg) gave (E)-1-(5-Methylspiro[2.5]oct-5-en-4-yl)but-2-en-1-one (0.354 g, 64%, 2 steps). Boiling point: 50° C. (0.07 mbar).

1. temperaturecooled to −78° C.
2. temperatureThe resulting solution was warmed to −20° C.
3. temperaturecooled to −78° C.
4. temperatureThe resulting solution was warmed to −10° C.
5. temperaturecooled to −78° C.
6. temperatureThe mixture was then warmed to 0° C.
7. extractionthe aqueous phase extracted three times with Et2O
8. washthe combined organic phases washed with a saturated aqueous solution of NaHCO3
9. dry with materiala saturated aqueous solution of NH4Cl, a saturated aqueous solution of NaCl, dried (Na2SO4)
10. concentrationconcentrated
11. dissolutionThe residue (596 mg) was dissolved in toluene (20 ml)
12. temperaturecooled
13. extractionThe aqueous phase was extracted three times with Et2O
14. washthe combined organic phases washed with a saturated aqueous solution of NH4Cl
15. concentrationa saturated aqueous solution of NaCl, and concentrated

ORD record

ord-708bc7dbc19842ad8aded844630ab864

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012391B2