Methyl iodide → Ethyl 2-methyl-4,4,4-trifluorobutyrate

Temperature

0 °C

A solution of diisopropylamine (19.5 mL) in tetrahydrofuran (200 mL) at 0° C. was treated with n-butyllithium (71 mL, 1.5M in hexanes). The resulting solution was stirred for 30 minutes at 0° C., then was cooled to -70° C. A solution of ethyl 4,4,4-trifluorobutyrate (14 mL) in tetrahydrofuran (150 mL) was slowly added to the lithium diisopropylamide solution and the resulting mixture was stirred at -70° C. for 30 minutes. A solution of iodomethane (11.5 mL) in tetrahydrofuran was added in one portion, the cooling bath was removed, and the reaction mixture was allowed to warm to room temperature. The reaction mixture was quenched with water and evaporated. The residue was dissolved in methylene chloride, washed (10% (w/v) hydrochloric acid, water, and brine), dried (MgSO4), filtered, and evaporated. The resulting pale yellow liquid was purified by distillation to yield ethyl 4,4,4-trifluoro-2-methylbutyrate as a colorless liquid (7.8 g, 46%); bp 125°-128 ° C.; partial NMR: (300 MHz, CDCl3): 1.30 (m, 6H, CH3), CH2CH3), 2.15 (m, 1H, H-C(3)), 2.64 (m, 1H, H-C(3)), 2.72 (m, 1H, H-C(2)), 4.16 (q, 2H, OCH2).

1. temperaturewas cooled to -70° C
2. stirringthe resulting mixture was stirred at -70° C. for 30 minutes
3. customthe cooling bath was removed
4. temperatureto warm to room temperature
5. customThe reaction mixture was quenched with water
6. customevaporated
7. dissolutionThe residue was dissolved in methylene chloride
8. washwashed (10% (w/v) hydrochloric acid, water, and brine)
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. customevaporated
12. distillationThe resulting pale yellow liquid was purified by distillation

ORD record

ord-995b62206657455a92dc2b6ed7cbbae9

Source dataset

uspto-grants-1994_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05286740