4-(2-Tetrahydropyranyloxy)phenylboronic acid

off-white to beige crystalline powder

THF (10 mL) was added to magnesium (abrasive) (24.3 g, 97.2 mmol) and two crystals of iodine (arbitrary amount), and the mixture was stirred at room temperature for 1 minute and then 4- (tetrahydro-2H- 2-yloxy) bromobenzene (25.0 g, 97.2 mmol) in THF (40.0 mL) was slowly added and the mixture was stirred at room temperature for 5 minutes under a nitrogen atmosphere, refluxed for 2 hours and returned to room temperature to obtain Grignard reagent Was prepared. Triethylborate (31.3 g, 292 mmol) and THF (600 mL) were added to another four-necked flask, and after purging with nitrogen, the mixture was cooled to -15 ° C.The Grignard reagent was cooled to 0 ° C. and added dropwise to a solution of triethylborate in THF over 30 minutes using a cannula. After completion of the dropwise addition, reaction was carried out for 1 hour while maintaining 0 ° C., whereby a gray solid precipitated. An ammonium chloride aqueous solution (10percent by weight, 150 mL) was added thereto, and the mixture was stirred at room temperature for 16 hours. Ethyl acetate (200 mL) was added and the mixture was stirred for a while. The organic layer was extracted, washed with water and saturated brine, dried over magnesium sulfate, magnesium sulfate was removed by filtration, and the solvent was distilled off under reduced pressure A pink solid was obtained. This was recrystallized from a mixed solvent of ethyl acetate and hexane 1: 10 (volume ratio) to obtain 4- (tetrahydro-2H-pyran-2-yloxy) phenylboronic acid (18.3 g) as a white solid (Yield 83percent).The compound obtained in Step 1(T-17) (723.7g, 2815.0mmol) in THF (3600ml)The solution was cooled to -40 , Was added dropwise n-BuLi (1.59M, 2290ml, 3659.0mmol).At -40 for 2 hours, Solution of triisopropoxyborane (688.16g, 3659.0mmol).Stirred at room temperature for 8 hours.The reaction mixture was poured into saturated aqueous ammonium chloride (4000ml), andExtracted with ethyl acetate.The extracts were washed with water (3000ml) and saturated brine (2000ml) cleaning, Dried over anhydrous magnesium sulfate, Concentrated under reduced pressure.The residue was recrystallized (heptane) to give compound(T-18) (203.12g, 914.77mmol, 32.5percent).In a reaction vessel purged with nitrogen, magnesium 3.62 g (0.15 mol) and 6 mL of tetrahydrofuran were added. The compound represented by formula (I-1b) 29.4 g (0.11 mol) in tetrahydrofuran was gradually added to prepare a Grignard reagent. Trimethyl borate 17.8 g (0.17 mol) in tetrahydrofuran was added dropwise and the mixture was stirred for 3 hours. 10percent hydrochloric acid was added dropwise to make the reaction acidic. After washing with saline, By distilling off the solvent, the compound represented by formula (I-1c) 24.3 g (0.10 mol) was obtained.adding the product of the previous step (9.16 mmol) to methanol, Substituted 5-trifluoromethylpyridine-2(1H)-one (4.58 mmol), After Et3N (18.32 mmol) and Cu(OAC) 2 (0.458 mmol) were heated and refluxed for 6 hours, the reaction solution was concentrated, dissolved in dichloromethane, and respectively, with 5% sodium hydroxide solution, Wash with saturated brine and dry with anhydrous sodium sulfate.After concentration and spin drying, the column was purified to give a white solid which was used for the next step.

suzuki reaction

Molecular Weight:222.05
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:222.1063391
Monoisotopic Mass:222.1063391
Topological Polar Surface Area:58.9
Heavy Atom Count:16
Complexity:204
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes