Hydrochloric Acid → 4-(4,4,4-Trifluorobutoxy)benzoic acid

Temperature

2.5 °C

55.00 g (0.408 Mol) 4,4,4-trifluorobutan-1-ol are dissolved in 550 ml tetrahydrofurane, 142 ml (0.102 Mol) triethylamine are added at room temperature. 38 ml (0.490 Mol) methanesulfonyl chloride were added dropwise under nitrogen. The mixture is stirred for 1 h at 0-5° C. The beige suspension is Hyflo-filtrated and washed with tetrahydrofurane. The filtrate is concentrated. The residue is dissolved in 1.4 l 1-methyl-2-pyrrolidone 62.70 g (0.408 Mol) of methyl 4-hydroxybenzoate and 226.00 g (1.43 Mol) of potassium carbonate are added to the lightly brown solution. The reaction suspension is allowed to react at 80° C. for 14 h. 1 l (1.0 Mol) of a 1N NaOH solution is added to the above mixture. The suspension is heated at reflux temperature for 30 min until the reaction is completed. The reaction mixture is allowed to cool at room temperature and thrown in cold water. The solution is carefully acidified with a 25% HCl solution and is stirred for 15 min. The product is filtrated off, washed with water and dried overnight at room temperature under vacuum to give 99.00 g (98%) of 4-(4,4,4-trifluorobutoxy)benzoic acid as a white solid.

1. filtrationThe beige suspension is Hyflo-filtrated
2. washwashed with tetrahydrofurane
3. concentrationThe filtrate is concentrated
4. additionare added to the lightly brown solution
5. customto react at 80° C. for 14 h
6. temperatureThe suspension is heated
7. temperatureat reflux temperature for 30 min until the reaction
8. temperatureto cool at room temperature
9. stirringis stirred for 15 min
10. filtrationThe product is filtrated off
11. washwashed with water
12. customdried overnight at room temperature under vacuum

ORD record

ord-1aa37931c1574bb088fc082a6145921e

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08557922B2