Methyl bromoacetate → HCID 594069, compound

Temperature

-30 °C

A three-neck, round-bottomed flask equipped with a dropping funnel and a septum, was charged with 6.6 mL (50 mmol) of beta-tetralone and 100 mL of THF under a nitrogen atmosphere. The solution was cooled to -30° C. and 36.6 mL (55 mmol) of LDA (1.5M in cyclohexane) was added dropwise. The solution was stirred for 30 minutes and warmed to 0° C. To this solution, 5.7 mL (60 mmol) of methyl bromoacetate was added. The solution was stirred at 0° C. for 1 h. The reaction was quenched with 3N HCl until pH of the mixture was <3. THF was removed in vacuo and the concentrate was extracted with methylene chloride (2×500 mL). The organic layer was washed with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow oil. This oil was purified by liquid chromatography on 560 g silica gel 60 (230°-400 m), eluting with hexane-ethyl acetate (4:1) and collecting 40 mL fractions. Fractions homogeneous by TLC were combined and concentrated in vacuo. The resulting oil needed the second chromatography to afford 8.22 g (75.4%) of >95% pure product as a near colorless oil.

1. customA three-neck, round-bottomed flask equipped with a dropping funnel
2. temperaturewarmed to 0° C
3. stirringThe solution was stirred at 0° C. for 1 h
4. customThe reaction was quenched with 3N HCl until pH of the mixture
5. customTHF was removed in vacuo
6. extractionthe concentrate was extracted with methylene chloride (2×500 mL)
7. washThe organic layer was washed with brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give a yellow oil
12. customThis oil was purified by liquid chromatography on 560 g silica gel 60 (230°-400 m)
13. washeluting with hexane-ethyl acetate (4:1)
14. customcollecting 40 mL fractions
15. concentrationconcentrated in vacuo

ORD record

ord-468cd570577749758c5581c33689e301

Source dataset

uspto-grants-1996_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05491236