Ethyl bromoacetate → HCID 18388310, compound

Temperature

-78 °C

Lithium bis(trimethylsilyl)amide (1.0 M hexane solution, 154.0 ml) was added dropwise to tetrahydrofuran (THF) (265 ml) at −78° C. in a nitrogen stream over a period of 25 minutes. A solution of ethyl bromoacetate (25.71 g) in THF (50 ml) was then added dropwise at −78° C. over a period of 15 minutes; a solution of 2-[bis(methylthio)methylene]cyclohexane-1,3-dione (25.62 g) in THF (240 ml) was further added drop by drop at −78° C. over a period of 30 minutes. After the reaction mixture was stirred at −78° C. for 1 hour and at room temperature for 15 hours, it was poured over an ice cooled saturated aqueous solution of ammonium chloride (1,250 ml) and stirred at room temperature for 15 minutes. The organic layer was separated; the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried (MgSO4), after which the solvent was distilled off. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (2:1, v/v) to yield an oily substance. The oily substance obtained was dissolved in diethyl ether (250 ml); a boron trifluoride-diethyl ether complex (25.21 g) was added at room temperature. After the reaction mixture was stirred at room temperature for 1 hour, it was poured over water (500 ml); the organic layer was separated; the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and dried (MgSO4), after which the solvent was distilled off. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:3, v/v) to yield ethyl 4,5,6,7-tetrahydro-3-methylthio-4-oxobenzo[c]furan-1-carboxylate (4.41 g, 14.6%), which was then recrystallized from ethyl acetate-hexane. Colorless plates. Melting point 123-124° C.

1. stirringstirred at room temperature for 15 minutes
2. customThe organic layer was separated
3. extractionthe aqueous layer was extracted with ethyl acetate
4. washwashed with water
5. dry with materialdried (MgSO4)
6. distillationafter which the solvent was distilled off
7. washeluted with ethyl acetate-hexane (2:1
8. customv/v) to yield an oily substance
9. customThe oily substance obtained
10. additiona boron trifluoride-diethyl ether complex (25.21 g) was added at room temperature
11. stirringAfter the reaction mixture was stirred at room temperature for 1 hour
12. customthe organic layer was separated
13. extractionthe aqueous layer was extracted with ethyl acetate
14. washwashed with water
15. dry with materialdried (MgSO4)
16. distillationafter which the solvent was distilled off
17. washeluted with ethyl acetate-hexane (1:3

ORD record

ord-c1b31b8c09a14b018954f514d9733d51

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06391905B1