Citric Acid → 4-Bromo-2-(trifluoromethyl)benzenethiol

Temperature

2.5 °C

4-Bromo-2-trifluoromethyl-benzenesulfonyl chloride (375 g, 1.16 mol) was dissolved in toluene (1.5 L) and a solution of triphenylphosphine (994 g, 3.79 mol) in toluene (1.5 L) was added at 5-10° C. within 45 min. The yellow suspension was stirred at 0-5° C. for min, then water (360 mL) was added at 5-12° C. (strongly exothermic) and the resulting colorless suspension was stirred for 20 min at room temperature. After filtration, the precipitate was washed with toluene (1 L). The combined organics were extracted with a potassium hydroxide solution (1M in water, 2.8 L). During extraction, 3 layers were formed. The upper layer was discarded, the other two were washed with toluene (1 L). The aqueous phase was acidified to pH 3-4 by addition of citric acid (280 g, 1.46 mol). After addition of n-heptane (1 L), the precipitate was filtered off and washed with n-heptane (500 mL). The layers of the combined filtrate were separated and the aqueous phase was extracted with n-heptane (1.5 L). The combined organic extracts were dried over sodium sulfate. Silica gel (250 g) was then added, the slurry was stirred for 10 min at room temperature, filtered and the filtered silica gel washed with n-heptane (1 L). The combined filtrate was concentrated and dried in vacuo at 45° C. to afford 291.2 g (98%) of the title compound as a colorless liquid that was used without further purification in the next step. MS (EI): m/z=256.9, 254.9 [M+H]+. 1H NMR (CDCl3, 400 MHz): δ 3.76 (q, J=2.8 Hz, 1H), 7.26 (d, J=8.3 Hz, 1H), 7.48 (dd, J=2.0 Hz, 8.5 Hz, 1H), 7.75 (d, J=1.9 Hz, 1H).

1. stirringwas stirred for 20 min at room temperature
2. filtrationAfter filtration
3. washthe precipitate was washed with toluene (1 L)
4. extractionThe combined organics were extracted with a potassium hydroxide solution (1M in water, 2.8 L)
5. extractionDuring extraction
6. custom3 layers were formed
7. washthe other two were washed with toluene (1 L)
8. filtrationthe precipitate was filtered off
9. washwashed with n-heptane (500 mL)
10. customThe layers of the combined filtrate were separated
11. extractionthe aqueous phase was extracted with n-heptane (1.5 L)
12. dry with materialThe combined organic extracts were dried over sodium sulfate
13. additionSilica gel (250 g) was then added
14. stirringthe slurry was stirred for 10 min at room temperature
15. filtrationfiltered
16. washthe filtered silica gel washed with n-heptane (1 L)
17. concentrationThe combined filtrate was concentrated
18. customdried in vacuo at 45° C.

ORD record

ord-82ae4168149a4586b00c42c0d86244f4

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796471B2