1,2-Dibromoethane → 2-Cyano-2-methyl-but-3-enoic acid tert-butyl ester

To a stirred slurry of sodium hydride (60% in mineral oil, 880 mg, 22 mmol) in dry N,N-dimethylformamide (100 mL) at 0° C., under nitrogen, was added dropwise cyano-methyl-acetic acid tert-butyl ester (prepared as in J. Am. Chem. Soc. 2011, 133, 8165, 3.10 g, 20 mmol). Any residual cyano-methyl-acetic acid tert-butyl ester was transferred by washing its original vessel with a little N,N-dimethylformamide and transferring to the reaction mixture. The reaction mixture was allowed to warm to ambient temperature for 40 minutes and then cooled to 0° C. 1,2-Dibromoethane (3.95 g, 1.81 mL, 21 mmol) was added dropwise via syringe pump over 30 minutes. The reaction mixture was stirred at 0° C. for a further 3 h and then allowed to warm to ambient temperature for 1 h. The mixture was poured into water and extracted with ethyl acetate (3×) and the combined organic extracts were washed with water (3×), dried over anhydrous magnesium sulfate, filtered and evaporated. To the residue was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3.14 g, 3.07 mL, 20.6 mmol) and the mixture stirred and heated to 80° C. for 30 minutes and then allowed to cool. Saturated ammonium chloride solution was added and the mixture extracted with diethyl ether (2×). The organic extracts were washed with 0.5 M Hydrochloric acid, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using iso-hexanes/ethyl acetate 19:1 to afford the title compound (3.15 g, 87%) as a pale yellow oil. 1H NMR (300 MHz, CDCl3) δ 1.52 (s, 9H), 1.68 (s, 3H), 5.37 (d, J=10.0 Hz, 1H), 5.63 (d, J=17.0 Hz, 1H), 5.89 (dd, J=17.0, 10.0 Hz, 1H).

1. washby washing its original vessel with a little N,N-dimethylformamide and transferring to the reaction mixture
2. temperaturecooled to 0° C
3. temperatureto warm to ambient temperature for 1 h
4. extractionextracted with ethyl acetate (3×)
5. washthe combined organic extracts were washed with water (3×)
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. customevaporated
9. stirringthe mixture stirred
10. temperatureheated to 80° C. for 30 minutes
11. temperatureto cool
12. extractionthe mixture extracted with diethyl ether (2×)
13. washThe organic extracts were washed with 0.5 M Hydrochloric acid, saturated sodium bicarbonate solution, saturated brine
14. dry with materialdried over anhydrous magnesium sulfate
15. filtrationfiltered
16. customevaporated
17. customThe residue was purified by silica gel chromatography

ORDレコード

ord-9c7376f16ec846deb80d853137735da8

出典データセット

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09145441B2