Sodium Bicarbonate → HCID 68771630, compound

Temperature

0 °C

At −70° C., a solution of diisopropylamine (0.5 g, 4.93 mmol) in tetrahydrofuran (4 ml) was treated with n-butyl lithium (3.3 ml, 1.6M in hexane, 5.14 mmol). The resulting solution was stirred at −70° C. for 20 min. and treated with a solution of 1-(rel-(6S,7R)-7-methylspiro[4.5]dec-8-en-6-yl)ethanone (0.79 g, 4.11 mmol) in tetrahydrofuran (4 ml). The resulting solution was stirred 20 min. at −70° C. warmed to 0° C., cooled to −70° C., and treated with a solution of acetaldehyde (0.9 g, 20.5 mmol) in tetrahydrofuran (4 ml). After 20 min. stirring, the reaction mixture was warmed to −5° C., treated with a 1:1 mixture of a 2N aqueous HCl solution and saturated aqueous NaCl solution (25 ml) and extracted three times with MTBE (60 ml). The combined organic phases were washed with a saturated solution of NaHCO3, with a saturated solution of NH4Cl, and with water, dried (MgSO4), and concentrated. Fluid chromatography (FC, SiO2, hexane/MTBE 35:1) of the crude product (1.3 g) gave the desired intermediate β-hydroxyketone (0.47 g, 1.98 mmol, 48%) which was dissolved in cyclohexane (1 ml). The resulting solution was treated with para-toluene sulfonic acid monohydrate (13 mg, 6.7 mmol) and refluxed 1.5 h. The reaction mixture was cooled to 0° C., treated with a saturated aqueous solution of NaHCO3 and the aqueous phase was extracted twice with MTBE. The combined organic phases were washed with water, dried (MgSO4) and concentrated. FC (SiO2, hexane/MTBE 50:1) of the crude product (0.42 g) gave (E)-1-(rel-(6S,7R)-7-Methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one (0.34 g, 79%).

1. temperaturerefluxed 1.5 h
2. extractionthe aqueous phase was extracted twice with MTBE
3. washThe combined organic phases were washed with water
4. dry with materialdried (MgSO4)
5. concentrationconcentrated

ORD record

ord-4164362a842545c0b496b38aada1c6b2

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012391B2