Diethyl Ether → 4-Cyano-3-(2,2,2-trifluoro-ethoxy)-benzoic acid methyl ester

Temperature

0 °C

CF3SO2Cl (2.7 ml, 25.5 mmol) was added under argon atmosphere to diethylether (60 ml) and cooled to 0° C. CF3CH2OH (1.8 ml, 25.5 mmol) and Et3N (3 ml, 21.25 mmol) were then added dropwise. The reaction mixture was stirred at 0° C. for 0.5 hour. The reaction was cooled to -20° C. to maximize ppt. of Et3N.HCl. The mixture was filtered and washed with cold diethylether (1×20 mL). The filtrate was concentrated to approx. 1/2 the volume in vacuo, keeping the flask at room temp. to minimize the loss of trifluoromethanesulfonic acid 2,2,2-trifluoro-ethyl ester. The resulting solution was treated with 4-cyano-3-hydroxybenzoic acid methyl ester. Example 34, Step 3 (1.5 g, 8.5 mmol) in DMF (28 ml) containing Cs2CO3 (5 g, 21.25 mmol). The reaction mixture stirred for several hours. The mixture was filtered and washed with DMF (3×5 mL). The solvent was removed in vacuo and the residue was purified by flash chromatography (5% EtOAc/Hexane) to yield the desired product.

1. temperatureThe reaction was cooled to -20° C.
2. filtrationThe mixture was filtered
3. washwashed with cold diethylether (1×20 mL)
4. concentrationThe filtrate was concentrated
5. customat room temp.
6. additionThe resulting solution was treated with 4-cyano-3-hydroxybenzoic acid methyl ester
7. stirringThe reaction mixture stirred for several hours
8. filtrationThe mixture was filtered
9. washwashed with DMF (3×5 mL)
10. customThe solvent was removed in vacuo
11. customthe residue was purified by flash chromatography (5% EtOAc/Hexane)

ORD record

ord-650ff5fae16a4a718df4c8f220e2996e

Source dataset

uspto-grants-2000_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06077853