Diethyl Ether → 2-Chloro-5-(trifluoromethyl)benzoic acid

A 250 mL pressure bottle was charged with 2-chloro-5-(trifluoromethyl)phenol triflate (20.6 mmol, 6.76 g), Pd(OAc)2 (1.71 mmol, 384 mg) and dppp (1.71 mmol, 701 mg). The flask was closed with a septum and evacuated three times with argon. Acetonitrile (114 mL), triethylamine (225.3 mmol, 30.7 mL) and water (22.2 mL) were added in succession with the aid of a syringe. The rubber septum was replaced with a teflon lined lid. The flask was pressurized with carbon monoxide (40 psi) and the gas was released. This process was repeated three times and finally the reaction was stirred for 5 min under pressure. The flask was then disconnected from the gas cylinder, immersed in a preheated oil bath (83-85° C.) and stirred for 2 h. The flask was re-pressurized with carbon monoxide and stirred for another 1 h. After the reaction mixture was cooled to room temperature, the pressure was released and it diluted with diethyl ether (250 mL) and 25 mL of 1.0 N NaOH. The sodium salt was extracted into water (2×100 mL). The combined aqueous extracts were acidified with 1.0 N HCl and extracted with diethyl ether (3×100 mL). The combined diethyl ether extracts were washed with brine, dried (MgSO4), filtered and the solution was concentrated in vacuo to furnish a light yellow solid. The solid was dissolved in diethyl ether (100 mL) and extracted with 1.0 N NaOH solution (2×50 mL). The combined aqueous layers were acidified and extracted with diethyl ether (2×100 mL). After the combined organic extracts were washed with brine (100 mL), the dried (MgSO4) solution was filtered and evaporated to dryness to give 1.6 g (35%) of 2-chloro-5-(trifluoromethyl)benzoic acid obtained as a colorless solid, mp 82-83.5° C . HR MS: Obs. mass, 223.9852. Calcd. mass, 223.9851 (M+).

1. customThe flask was closed with a septum
2. customevacuated three times with argon
3. customimmersed in a preheated oil bath
4. stirring(83-85° C.) and stirred for 2 h
5. stirringstirred for another 1 h
6. extractionThe sodium salt was extracted into water (2×100 mL)
7. extractionextracted with diethyl ether (3×100 mL)
8. washThe combined diethyl ether extracts were washed with brine
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationthe solution was concentrated in vacuo
12. customto furnish a light yellow solid
13. extractionextracted with 1.0 N NaOH solution (2×50 mL)
14. extractionextracted with diethyl ether (2×100 mL)
15. washAfter the combined organic extracts were washed with brine (100 mL)
16. dry with materialthe dried (MgSO4) solution
17. filtrationwas filtered
18. customevaporated to dryness

ORD record

ord-6500e6eceb5b43088665a7a4b7199095

Source dataset

uspto-grants-2002_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06479666B2