Ethyl chloroformate → 4,4,4-Trifluoro-2-(triphenyl-lambda5-phosphanylidene)-butyric acid ethyl ester

Temperature

-5 °C

A suspension of (3,3,3-trifluoropropyl)triphenylphosphonium iodide (194.5 g, 0.4 mol) in THF (anhydrous, 800 mL) was cooled to −5° C. in an ice/brine bath under nitrogen. To this suspension, lithium bis(trimethylsilyl)amide (1.0 M in THF, 800 mL, 0.8 mol) was added drop-wise over 2 h. The temperature was maintained below 5° C. throughout the addition. The reaction mixture was then cooled to −75° C. in a dry ice/acetone bath. To this solution, ethylchloroformate (76.5 mL, 0.8 mol) was added drop-wise over 30 min. The reaction was stirred at −75° C. for an additional hour and allowed to warm to 25° C. overnight. The reaction mixture was poured onto brine (1.5 L) and stirred for 30 min. The layers were separated and the organic layer was washed with brine (200 mL). The aqueous layer was washed with CH2Cl2 (2×200 mL) and the combined organics were concentrated to a residue. This residue was redissolved in CH2Cl2 (500 mL), dried over MgSO4, and filtered through a plug of magnasol. The solvent was reduced to a minimum (˜100 mL) in vacuo and the product was precipitated with hexanes (250 mL). The solvent was completely removed in vacuo and the solid product was triturated with hexanes (500 mL). The solid was isolated by filtration and dried overnight in vacuo at 25° C. to give a beige powder (152.8 g, 89%).

1. temperatureThe temperature was maintained below 5° C. throughout the addition
2. temperatureThe reaction mixture was then cooled to −75° C. in a dry ice/acetone bath
3. temperatureto warm to 25° C. overnight
4. additionThe reaction mixture was poured onto brine (1.5 L)
5. stirringstirred for 30 min
6. customThe layers were separated
7. washthe organic layer was washed with brine (200 mL)
8. washThe aqueous layer was washed with CH2Cl2 (2×200 mL)
9. concentrationthe combined organics were concentrated to a residue
10. dissolutionThis residue was redissolved in CH2Cl2 (500 mL)
11. dry with materialdried over MgSO4
12. filtrationfiltered through a plug of magnasol
13. customthe product was precipitated with hexanes (250 mL)
14. customThe solvent was completely removed in vacuo
15. customthe solid product was triturated with hexanes (500 mL)
16. customThe solid was isolated by filtration
17. customdried overnight in vacuo at 25° C.

ORD record

ord-405ba401ec1747aca7342f8347d3d83f

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07550629B2