4-CHLORO-3-(TRIFLUOROMETHYL)BENZYL ALCOHOL

colorless to light yellow liquid

A. Under nitrogen protection conditions, Add 20 mmol of 3-trifluoromethyl-4-chlorophenylethanol to the reaction flask in turn.40mmol PhICl2, 70mmol NaN3, 0.26 mmol of tetrabutylammonium bromide (TBAB) and 100 mL of tetrahydrofuran, Stir at 0 ° C for 2 h, then place in an oil bath at 80 ° C for 4 h.After the TLC monitoring reaction was completed, 50 mmol of intermediate I was added to the two vials.Stirring was continued for 2 h at 80 ° C. After the reaction was completed, The reaction system was cooled to room temperature, and the reaction solution was added to 60 mL of water.And 40 mL of ethyl acetate in a mixed solvent, stirred, layered, The aqueous phase was extracted once with ethyl acetate and ethyl acetate was combined.Wash with 50 mL of saturated sodium chloride, drain, and dry at 40 ° C under vacuum.The crude product of sorafenib was 9.0 g, and the yield was 96.8percent.General procedure: To a solution of alcohol (1mmol) in freshly distilled THF (5ml) was added triphenylphosphine (1.1mmol) and N-hydroxylphthalimide (1.1mmol). After the solution was cooled to 0°C diisopropylazodicarboxylate (1.1mmol) was added dropwise. The solution was allowed to warm to room temperature over 3h. Reaction progress was monitored by TLC (1:1 heptanes:ethyl acetate). Hydrazine monohydrate (1.1mmol) was then added and the solution was allowed to stir for 30min. The resulting reaction mixture was filtered to remove the white precipitate. The filtrate was concentrated and subjected to flash chromatography (1:1 heptanes/ethyl acetate). The resulting product was dissolved in ether and treated with HCl (2.0M solution in ether) to afford the HCl salt of the O-alkylhydroxylamine. Contaminating diisopropyl hydrazinodicarboxylate could be washed away from the HCl salt with dichloromethanePreparation 612, 5-Difluoro-4-[4-chloro-3-(trifluoromethyl)phenylmethoxy1-benzonitrileTo a sol ution of 4-chloro-3-(thfluoronnethyl)-benzylalcohol (0.27 g, 1 .28 mmol) and 2, 4, 5-trifluorobenzonitrile (0.2 g, 1 .28 mmol) in DMSO (5 mL) was added potassium carbonate (0.33 g, 0.25 mmol). The resulting mixture was stirred at room temperature for 18 hours. The reaction mixture was partitioned between water (15 mL) and EtOAc (20 mL). The organic layer was separated, dried over magnesium sulphate, filtered and evaporated to yield the title compound (0.43 g, 97percent).1H NMR (CD3OD, 400 MHz): delta 5.28 (s, 2H), 7.30 - 7.38 (m, 1 H), 7.55 - 7.75 (m, 3H), 7.90 (s, 1 H).Molecular ion not observed

Molecular Weight:210.58
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:210.0059270
Monoisotopic Mass:210.0059270
Topological Polar Surface Area:20.2
Heavy Atom Count:13
Complexity:171
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes