3-(Trifluoromethoxy)phenol

Clear colorless to yellow liquid

A mixture of To a souton of 3- (trfluoromethoxy) pheno (4.0 g, 23 mmo) fl dry THF (16 mL) at 0 °C was added potassium tert-butoxde, portonwse (10g. 90 mmo) over 15 mnutes w[th vigorous strrng, The reaction was then warmed to 0 °C and sfirred for 30 mn. The reaction wascooed to 0 °C and choromethy methy ether (4.3 niL, 56 mmo) was added dropwse, After the add Won, the sDrrng was contnued for another 4h at rt. The reacUon mxture was duted w[th water and extracted with EtOAc, dried (Na2SO4), ifitered and concentrated. PurWcation (FCC. SO2 0 10percent EtOAc/hexanes) afforded the tWe compound as an o (5.0 g, 62percent yed). 1H NMR (400 MHz, CDC3): oe 7.32 7.24 (m, I H), 7.01 6.94 (m, I H), 6.94'6.90 (m, IH), 6.89 '6.82 (m, 1H), 5.17 (5, 2H).l- enel - ethoxymethoxy-3-trifluoiOmethoxy-benzeneTo a solution of 3-Trifluoromethoxy phenol (5.0 g, 28.08 mmol, ) in dry Ti l l- (20m L)was added 4A molecular sieves (10 g) and the reaction mixture was cooled to -5 0 C. Then Potassium tert -butoxide (12.5 g, 1 12 mmol, ) was added to this cold reaction mixture which was then warmed to RT and stirred for 30 min. Again the reaction mass was cooled to -5 C and MOMC1 (4.5 ml, 56.0 mmol, 2.0 eqv) was added drop wise. After the addition the reaction was continued for another 2h at RT. Reaction mixture was diluted with water ( 1 50ml) and extracted with diethylether (200ml X 2), washed with water, brine. dried over Na2S04 and evaporated the solvent. The yellow oily crude was purified by column chromatography (Neutral AI203, Hexane) to afford l-(Methoxymethoxy)-3- (tritluoromethoxy) benzene in 60percent yield.LC/ S [ -l-l] + 221.2, ?-NMR (400 MHz, DMSO d6) delta (ppm): 7.383-7.424(1, 1 H, J=8.0 I Iz); 7.040-7.058(d, lH, J=7.2 Hz );6.954-6.977 (d, 2H, J=9.2 Hz) ; 5.214 (s, 2H, ); 3.3365 g of To a suspension of 20.0 g of A mixture of 2, 4, 5-tribromo-1-[(4-chlorophenyl)methyl]-1H-imidazole (175 g, 407.61 mmol, 1 equiv.), General procedure: To a mixture of NaH (60% in mineral oil, 0.050 g, 1.23 mmol) inanhydrous THF (2 mL) at 0 C under Ar atmosphere was added asolution of the differently substituted phenol or thiophenol(1.11 mmol) in 1mL of anhydrous THF. This mixture was stirred atr.t. for 20 min. A solution of the different intermediate 24e32(0.74 mmol) in anhydrous THF (3 mL) was added slowly. The reactionmixture was stirred at r.t. overnight. The mixture was thendiluted with ethyl acetate (30 mL), washed with brine (15 mL), water (30 mL), and dried over Na2SO4 and concentrated undervacuum. The crude residue was purified by flash column chromatographyor via Biotage Isolera 1.

Molecular Weight:178.11
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:178.02416388
Monoisotopic Mass:178.02416388
Topological Polar Surface Area:29.5
Heavy Atom Count:12
Complexity:146
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes