Hydrochloric Acid → Benzenethiol, 2-amino-3,4,6-trifluoro-, hydrochloride

Temperature

125 °C

A solution of 4,5,7-trifluoro-2-methylbenzothiazole (25.0 g, 123 mmol) in ethylene glycol (310 mL, 0.4 M) and 30% aq. NaOH (310 mL, 0.4 M) was degassed using a nitrogen stream then heated to a gentle reflux (125° C.) for 3 h. The solution was cooled to 0° C. and acidified to pH 3-4 using conc. HCl (approx. 200 mL). The solution was extracted with ether (750 mL) and washed with water (200 mL). The organic layer was dried over Na2SO4, filtered and treated with 2,2-di-tert-butyl-4-methylphenol (0.135 g, 0.5 mol %). After concentrating to dryness, the crude product was dissolved in anhydrous methanol (200 mL) and treated with an HCl solution in 1,4-dioxane (37 mL, 4 N, 148 mmol). The resulting mixture was concentrated to dryness, triturated with isopropylether (100 mL) and filtered to give 2-amino-3,4,6-trifluorothiophenol hydrochloride (19.3 g, 73%) as a light brown solid that was used without further purification. mp. 121-124 C; Rf 0.43 (30% ethyl acetate in heptane); Anal. Calcd for C6H5ClF3NS: C, 33.42; H, 2.34; N, 6.50; S, 14.87. Found C, 33.45; H, 2.27; N, 6.48; S, 14.96.

1. temperaturethen heated to
2. temperatureThe solution was cooled to 0° C.
3. extractionThe solution was extracted with ether (750 mL)
4. washwashed with water (200 mL)
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. additiontreated with 2,2-di-tert-butyl-4-methylphenol (0.135 g, 0.5 mol %)
8. concentrationAfter concentrating to dryness
9. dissolutionthe crude product was dissolved in anhydrous methanol (200 mL)
10. concentrationThe resulting mixture was concentrated to dryness
11. customtriturated with isopropylether (100 mL)
12. filtrationfiltered

ORD record

ord-ed09315b92504021b476706db407390a

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07304079B2