Hydrochloric Acid → HCID 86663800, compound

Temperature

5 °C

With stirring in a nitrogen atmosphere, a mixture of 111 g of 1,1,1,3,3,3-hexafluoro-2-propanol and 700 ml of tetrahydrofuran was cooled below −40° C., to which 500 ml of a n-hexane solution of 2.64M n-butyllithium was added dropwise. At the temperature, the reaction mixture was stirred for 30 minutes. The cooling bath was changed to ice cooling, allowing the reaction mixture to warm to 5° C. A mixture of 50 g of isovaleraldehyde and 50 ml of tetrahydrofuran was added dropwise. With stirring, the reaction mixture was warmed up to room temperature, after which stirring was continued for a further 5 hours. The reaction mixture was poured into dilute hydrochloric acid and extracted with ether. The ether solution was washed, dried, and concentrated, obtaining crude 1,1,1,3,3-pentafluoro-4-hydroxy-2-heptanone. The crude product was combined with 50 g of water at room temperature, to which 100 g of 25 wt % sodium hydroxide aqueous solution was added. The mixture was stirred overnight at room temperature. With stirring, the mixture was slowly heated to 90° C. After cooling, the reaction mixture was extracted with n-hexane, with the hexane layer being discarded. The water layer was made acidic by adding 20 wt % hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate solution was dried and concentrated, obtaining 107 g (qualitative yield) of the target compound, 2,2-difluoro-3-hydroxy-5-methylhexanoic acid (Intermediate 1). This crude product had a sufficient purity as an intermediate and was ready for use in the subsequent step.

1. additionwas added dropwise
2. stirringAt the temperature, the reaction mixture was stirred for 30 minutes
3. additionwas added dropwise
4. stirringWith stirring
5. temperaturethe reaction mixture was warmed up to room temperature
6. stirringafter which stirring
7. extractionextracted with ether
8. washThe ether solution was washed
9. customdried
10. concentrationconcentrated

ORD record

ord-986f320cbf6e4ee089d2e6a4e7f4f278

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697903B2