Allyl bromide → 7-Allyl-1,4-dioxa-spiro[4.5]decane-7-carboxylic acid ethyl ester

Temperature

-20 °C

Then, to a round bottom flask was added N,N-diisopropylamine (3.97 mL, 28.4 mmol) and THF (22.1 mL). The mixture was cooled at −20° C. 1.6 M of n-butyllithium in hexane (15.8 mL) was added. The crude mixture was stirred at 0° C. for 30 min and then cooled down at −20° C., and 1,4-dioxa-spiro[4.5]dicane-7-carboxylic acid ethyl ester (4.50 g, 21.0 mmol) from step 1 was added dropwise. The mixture was stirred at 0° C. for 30 min, and then cooled at −20° C., and allyl bromide (2.00 mL, 23.1 mmol) was added. The mixture was warmed up to rt slowly and stirred at rt for 30 min. The reaction mixture was quenched with ice, diluted with ethyl acetate (60 mL), and washed sequentially with 1N aqueous HCl (5 mL), water and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford 4.30 g (81%) of the title compound, 7-allyl-1,4-dioxa-spiro[4.5]decane-7-carboxylic acid ethyl ester, as a yellow oil. It was used in the next step without further purification. 1H NMR (400 MHz, CDCl3): δ5.64-5.74 (m, 1H), 4.97-5.05 (m, 2H), 4.05-4.17 (m, 2H), 3.82-3.99 (m, 4H), 2.34-2.41 (m, 1H), 2.27 (dt, J=13.6, 2.1 Hz, 1H), 2.08-2.16 (m, 2H), 1.76-1.88 (m, 1H), 1.60-1.72 (m, 2H), 1.46-1.54 (m, 1H), 1.42 (d, J=13.6 Hz, 1H), 1.25 (t, J=7.1 Hz, 3H), 1.08-1.16 (m, 1H).

1. temperaturecooled down at −20° C.
2. temperaturecooled at −20° C.
3. temperatureThe mixture was warmed up to rt slowly
4. stirringstirred at rt for 30 min
5. customThe reaction mixture was quenched with ice
6. additiondiluted with ethyl acetate (60 mL)
7. washwashed sequentially with 1N aqueous HCl (5 mL), water and brine
8. dry with materialThe organic layer was dried over Na2SO4
9. concentrationconcentrated under reduced pressure

ORD record

ord-9f002da50aa6404288b90bff07d35593

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08633190B2