Ethyl isobutyrate → Ethyl 2,2-dimethyl-7-(tetrahydro-2H-pyran-2-yloxy)heptanoate

Temperature

0 °C

A solution of diisopropylamine (1.78 mL) in dry THF (10 mL) at 0° C. under nitrogen was treated dropwise with n-butyl lithium (2.5M in hexanes, 5.09 mL) to generate a pale yellow solution which was stirred at 0° C. for 30 minutes then cooled to −78° C. and treated dropwise with ethyl isobutyrate (1.55 mL). The solution was stirred at −78° C. for 45 minutes then a solution of 2-(5-bromopentyloxy)tetrahydro-2H-pyran (example 285, step a) (3.20 g) in dry THF (1 mL) was added dropwise. The reaction mixture was stirred at −78° C. for 10 minutes then was allowed to warn to room temperature overnight. The reaction mixture was cooled to 0° C. then treated with saturated aqueous ammonium chloride solution (3 mL) and extracted with ethyl acetate. The aqueous phase was extracted with ethyl acetate (×2) and the combined organic phase was washed with water, saturated aqueous sodium bicarbonate solution and brine then dried over sodium sulfate, filtered and evaporated. Purification was by silica gel chromatography eluting with 0-5% ethyl acetate in cyclohexane to afford the subtitled compound as colourless liquid. Yield 2.22 g.

1. temperaturethen cooled to −78° C.
2. stirringThe solution was stirred at −78° C. for 45 minutes
3. stirringThe reaction mixture was stirred at −78° C. for 10 minutes
4. waitto warn to room temperature overnight
5. temperatureThe reaction mixture was cooled to 0° C.
6. extractionextracted with ethyl acetate
7. extractionThe aqueous phase was extracted with ethyl acetate (×2)
8. washthe combined organic phase was washed with water, saturated aqueous sodium bicarbonate solution and brine
9. dry with materialthen dried over sodium sulfate
10. filtrationfiltered
11. customevaporated
12. customPurification
13. washeluting with 0-5% ethyl acetate in cyclohexane

ORD record

ord-731e78ef0ee5439ba1a4d7a8dcb827f0

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629271B2