Methyl iodide → Ethyl (4E)-2,4-dimethyl-5-(4-methylphenyl)-4-pentenoate

Temperature

-78 °C

n-Butyl lithium (1.6 M in hexanes from Fluka, 70 ml, 0.111 mol) was added rapidly to a solution of diisopropylamine (11.7 g, 0.116 mol) in dry THF (200 ml) under nitrogen, maintaining the temperature below −20° C. by cooling in a dry ice-acetone bath. After cooling to −78° C., dry DMPU (14.9 g, 0.116 mol) was added drop-wise for 5 minutes. Then, ethyl (4E)-4-methyl-5-(4-methylphenyl)-4-pentenoate (21.5 g, 0.092 mol) was added in 10 minutes. The reaction was warmed up to 0° C. and kept for 20 minutes at this temperature before cooling back to −78° C. Methyl iodide (66 g, 0.46 mol) was added drop-wise. The reaction was warmed up to room temperature and stirred overnight. It was then poured onto water and extracted twice with diethyl ether. Each organic fraction was washed with water and brine. Combined extracts are dried over solid anhydrous sodium sulfate. The solid was filtered off, rinsed with diethyl ether. Solvents are removed under vacuum and the product was purified by bulb-to-bulb distillation (125° C./0.04 mbar). 18.5 g of colorless liquid were obtained (yield=81%).

1. temperaturemaintaining the temperature below −20° C.
2. temperatureby cooling in a dry ice-acetone bath
3. temperatureThe reaction was warmed up to 0° C.
4. temperaturebefore cooling back to −78° C
5. temperatureThe reaction was warmed up to room temperature
6. additionIt was then poured onto water
7. extractionextracted twice with diethyl ether
8. washEach organic fraction was washed with water and brine
9. dry with materialCombined extracts are dried over solid anhydrous sodium sulfate
10. filtrationThe solid was filtered off
11. washrinsed with diethyl ether
12. customSolvents are removed under vacuum
13. distillationthe product was purified by bulb-to-bulb distillation (125° C./0.04 mbar)

ORD record

ord-d41f85ab376e42b9aa774a59e86db3e8

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815792B2