Chlorotrimethylsilane → (+/-)-ethyl 2-(1-methyl-2,3-dihydro-1H-inden-1-yl)acetate

Temperature

-78 °C

To a suspension of copper iodide (1.9 g, 9.9 mmol) in diethyl ether (10 mL) was added methyl lithium (12.4 mL, 19.8 mmol, 1.6M in diethyl ether) at 0° C. and the mixture was stirred for 10 min. The solvent was removed under reduced pressure at 0° C. and then CH2Cl2 (10 mL) was added. The reaction mixture was stirred for 5 minutes at 0° C., and then the solvent was removed again under reduced pressure at 0° C. To the residue was added pre-cooled CH2Cl2 (75 mL), cooled to −78° C., and then added trimethylsilyl chloride (1.3 mL, 9.9 mmol) and a solution of a mixture of (E)-ethyl 2-(2,3-dihydro-1H-inden-1-ylidene)acetate and ethyl 2-(1H-inden-3-yl)acetate (1:1 mixture, 1 g, 4.9 mmol) in CH2Cl2 (10 mL), successively. The resulted mixture was allowed to warm to room temperature and stirred overnight. The reaction was quenched by addition of a mixture of aqueous saturated NH4Cl and 28% NH4OH (1:1, 50 mL). The mixture was extracted with diethyl ether (3×50 mL) and the combined extracts were washed with water, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (Hexanes-EtOAc, 0 to 10%) to give 0.47 g of the title compound. Additionally, 0.17 g of unreacted ethyl 2-(1H-inden-3-yl)acetate was recovered. MS (DCI/NH3) m/z 236 (M+NH4)+.

1. customThe solvent was removed under reduced pressure at 0° C.
2. additionCH2Cl2 (10 mL) was added
3. stirringThe reaction mixture was stirred for 5 minutes at 0° C.
4. customthe solvent was removed again under reduced pressure at 0° C
5. additionTo the residue was added
6. temperaturepre-cooled CH2Cl2 (75 mL)
7. temperatureto warm to room temperature
8. stirringstirred overnight
9. customThe reaction was quenched by addition of a mixture of aqueous saturated NH4Cl and 28% NH4OH (1:1, 50 mL)
10. extractionThe mixture was extracted with diethyl ether (3×50 mL)
11. washthe combined extracts were washed with water
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe crude product was purified by flash chromatography (Hexanes-EtOAc, 0 to 10%)

ORD record

ord-f3e3d4c32cb342f2bd85a5f6ec14cf88

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609669B2