3,3,3-Trifluoropropyne → ethyl 4-trifluoroprop-1-ynylbenzoate

Temperature

-78 °C

3,3,3-Trifluoro-1-propyne (approx. 0.6 mL, approx. 6 mmol) was condensed in a flame-dried Schlenk tube immersed in a dry ice/acetone bath. Tetrahydrofuran (3 mL) was added followed by a solution of butyllithium in hexanes (2.15 mL, 3.44 mmol, 1.6 M). After stirring 2.5 h at −78° C., zinc chloride (6.87 mL, 3.44 mmol, 0.5 M solution in tetrahydrofuran) was added to the reaction mixture and the reaction vessel was transferred to an ice-water bath and maintained at 0° C. for 30 min. Ethyl 2-ethoxy-4-iodobenzoate (1.00 g, 3.12 mmol, prepared as described in example 14) and tetrakis(triphenylphosphine)palladium(0) (0.18 g, 0.16 mmol) were then added. The reaction vessel was allowed to warm to room temperature and then after 1 h warmed to 50° C. for 18 h. After cooling, the reaction mixture was partitioned between brine (70 mL) and methylene chloride (2×100 mL), dried over magnesium sulfate and evaporated. Purification of the crude residue by flash column chromatography (silica gel, eluting with 1/1 mixture of methylene chloride and hexanes) gave ethyl 4-trifluoroprop-1-ynylbenzoate as an off-white solid (0.474 g, 53%).

1. customcondensed in a flame-dried Schlenk tube
2. customimmersed in a dry ice/acetone bath
3. customthe reaction vessel was transferred to an ice-water bath
4. temperaturemaintained at 0° C. for 30 min
5. temperatureto warm to room temperature
6. temperatureafter 1 h warmed to 50° C. for 18 h
7. temperatureAfter cooling
8. customthe reaction mixture was partitioned between brine (70 mL) and methylene chloride (2×100 mL)
9. dry with materialdried over magnesium sulfate
10. customevaporated
11. customPurification of the crude residue
12. washby flash column chromatography (silica gel, eluting with 1/1 mixture of methylene chloride and hexanes)

ORD record

ord-c77a61c3c64748c7befadbbb1bec093e

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07579368B2