Acetonitrile → 3,3,3-Trifluoro-2,2-dimethylpropanoic acid

温度

70 °C

Reaction was carried out in two separate batches, employing 3.85 g of methyl 3,3,3-trifluoro-2,2-dimethylpropanoate in each batch. To a stirred refluxing suspension of sodium hydride (1.41 g of a 60% dispersion in mineral oil, 35 mmol) in dry THF (30 mL) (under an argon atmosphere) was added a mixture of crude methyl 3,3,3-trifluoro-2,2-dimethylpropanoate (3.85 g) and dry acetonitrile (1.85 mL, 35 mmol), dropwise over the course of 45 mins. The resulting pale yellow suspension was heated at 70° C. for a further 15 h. After cooling to rt, both reaction batches were combined whereupon the solvent was removed in vacuo. The resulting orange foam was redissolved in water (200 mL) and washed with diethyl ether (2×200 mL), to remove residual mineral oil. The aqueous layer was separated, acidified to pH 2 with aqueous 2N hydrochloric acid and extracted with diethyl ether (3×200 mL). The combined ether layers were dried over MgSO4, filtered, then concentrated under reduced pressure to afford 5,5,5-trifluoro-4,4-dimethyl-3-oxopentanenitrile as a yellow oil (4.27 g, 37% from 3,3,3-trifluoro-2,2-dimethylpropionic acid) which was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 3.77 (s, 2H), 1.43 (s, 6H).

1. customReaction
2. customseparate batches
3. temperatureTo a stirred refluxing
4. additionsuspension of sodium hydride (1.41 g of a 60% dispersion in mineral oil, 35 mmol) in dry THF (30 mL) (under an argon atmosphere)
5. additionwas added
6. customdropwise over the course of 45 mins
7. temperatureAfter cooling to rt
8. customboth reaction batches
9. customwas removed in vacuo
10. dissolutionThe resulting orange foam was redissolved in water (200 mL)
11. washwashed with diethyl ether (2×200 mL)
12. customto remove residual mineral oil
13. customThe aqueous layer was separated
14. extractionextracted with diethyl ether (3×200 mL)
15. dry with materialThe combined ether layers were dried over MgSO4
16. filtrationfiltered
17. concentrationconcentrated under reduced pressure

ORDレコード

ord-aeb82c08f35b4768b6fdc6966e6423dc

出典データセット

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09320739B2