Ethyl isobutyrate → Ethyl 8-(tert-butyldimethylsilyloxy)-2,2-dimethyloctanoate

Temperature

-78 °C

n-Butyl lithium (32.8 mL) was added to a solution of diisopropylamine (1M in toluene, 11.64 mL) in THF (60 mL) at 0° C. to 5° C. over 15 minutes, and this mixture was stirred for 30 minutes. The reaction mixture was cooled to −78° C. then isobutyric acid ethyl ester (10 mL) was added dropwise over 15 minutes. The mixture was stirred at −78° C. for 1 hour, then (6-bromohexyloxy)-tert-butyldimethylsilane (23 mL) was added dropwise and the reaction mixture was stirred at −78° C. for a further 60 minutes. The cooling bath was removed and the mixture stirred at room temperature overnight before being poured onto a saturated aqueous solution of ammonium chloride (300 mL) and extracted with ethyl acetate (2×300 mL). The combined organic layers were washed with water (250 mL), dried over magnesium sulfate, filtered and evaporated to give the crude product. Purification was by silica gel chromatography eluting with 0-40% ethyl acetate in cyclohexane to afford the subtitled compound as a pale amber liquid. Yield 20 g.

1. stirringThe mixture was stirred at −78° C. for 1 hour
2. stirringthe reaction mixture was stirred at −78° C. for a further 60 minutes
3. customThe cooling bath was removed
4. stirringthe mixture stirred at room temperature overnight
5. additionbefore being poured onto a saturated aqueous solution of ammonium chloride (300 mL)
6. extractionextracted with ethyl acetate (2×300 mL)
7. washThe combined organic layers were washed with water (250 mL)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. customevaporated
11. customto give the crude product
12. customPurification
13. washeluting with 0-40% ethyl acetate in cyclohexane

ORD record

ord-5880a2792b5349f291934c317f630d26

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148373B2