2,4-BIS(TRIFLUOROMETHYL)TOLUENE synthesis

Yield:251651-23-7 77%

Reaction Conditions:

with N-Bromosuccinimide;sulfuric acid;trifluoroacetic acid at 20; for 48 h;

Steps:

17.1

2, 4-Bis (trifluoromethyl) toluene (22a, 12.7g, 56 mmol) was placed in a round-bottom flask. Then 28 ml TFA and 7.8 ml H₂SO₄ (28% of the amount of TFA) were added. NBS (10. Og, 56 mmol, leq) was added to the reaction mixture in small portions. The reaction was allowed to run at ambient temperature over two days. After 48h the reaction was worked up. The reaction mixture was poured out to ice cold water (200ml) and the organic layer (oily residue) was separated from water layer by extraction with Et₂O. Ether layer was washed with saturated NaHCO₃ aqueous solution and then the layers were separated. The organic layer was collected, dried over Na₂SO₄ and the solvent was removed. The pure product (13. Ig, 77% yield) as a slightly yellow oil was collected.Structure determination:RP-HPLC Conditions: HP 1100 HPLC chromatograph, Waters 3.9 x 150 mm NovaPak HR C18 column with guard column, 0.010 mL injection, 1.5 mL/min, 1.500 mL injection loop, 254 nm detection, A = water (0.1% v/v TFA) and B = MeCN (0.1% v/v TFA) , gradient 10% B 1 min, 10-80% B over 9 min, 80-100% B over 1 min, 100 %B 1 min, retention time 12.3 min. ¹H NMR (400 MHz, CDCl₃): δ 2.54 (s, 3H), 7.64 (s, IH), 8.00 (s, IH).

References:

WO2008/66921,2008,A2 Location in patent:Page/Page column 64-65