4'-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)ACETANILIDE

Light yellow to light beige powder

To a solution of compound 47 (250 mg, 1.45 mmol) in dioxane(6 mL) at room temperature was added bis(pinacolato)diboron(554 g, 2.18 mmol, 1.5 equiv.), and KOAc (427 mg, 4.35 mmol, 3equiv.). The reaction mixture was degassed under N2. Pd(dppf)Cl2(90 mg, 0.12 mmol, 0.1 equiv.) was added to the mixture anddegassed under N2. The reaction mixture was heated to 100 C andstirred overnight under nitrogen. The reaction mixture was monitoredusing TLC until completion, filtered through Celite andwashed with EA. The reaction solvent was evaporated underreduced pressure to give a residue, which was purified via silica gelcolumn chromatography (elution system - EA/Hexane 1: 1) togive compound 48 as a white solid (870 mg, 71percent).Rf 0.43 (EA/Hexane 1: 1); 1H NMR (400 MHz, CDCl3) d 7.76(d, J 8.3 Hz, 2H), 7.51 (d, J 7.9 Hz, 2H), 7.19 (s, 1H), 2.18 (s, 3H), 1.33 (s, 12H).To a stirred solution of CI (300 mg, 1.14 mmol) in DMSO (15 mL) under inert atmosphere were added bis(pinacalato)diboron (321 mg, 1.26 mmol) and fused potassium acetate (338 mg, 3.44 mmol) at RT. The reaction was purged with argon for 30 min. Then Pd(dppf)[00168] To 25 mg PdCl2(dppf).CH2Cl2 in a reaction tube under nitrogen were added 4 ml dioxane, 0.43 ml (3 mmol) triethylamine, 0.47 ml (3.2 mmol) pinacolborane and 262 mg (1.0 mmol) p-iodoacetanilide. The p-iodoacetanilide did not react with the pinacolborane to liberate hydrogen. The reaction solution was warmed to 80 C. with stirring in an oil bath. After 1 h the solution had darkened and an aliquot (0.3 ml) was removed from the reaction solution, extracted into diethyl ether, washed several times with water and analysed by gc (fid detector, SGE HT5 capillary column). There was only one strong peak (of area 74percent of total peak areas, uncorrected for response factors) in the gc and that was shown by gc/ms to be due to the desired arylboronic acid pinacol ester. On heating the reaction mixture for a further 4 h at 80 C., the apparent yield of the required boronic acid ester increased to 81percent while that of the acetanilide and phenylboronic acid pinacol ester peak areas were 14percent and 3.4percent respectively.[00240] The catalyst amount in this reaction was reduced to approx. {fraction (1/35)} that used in the small scale reactions. The molar ratio of catalyst:iodide:pinacolborane:NEt3 is 1:1150:1500:2933. The amount of pinacolborane was 1.25 equivalents compared to the iodide. The pinacolborane was made from BH3'e2 by reaction with pinacol in dioxane. 50 ml of BH3'e2 were dissolved in 100 ml of dioxane in a 1 L Schlenk flask. To this was added dropwise 63.0 g of pinacol in 140 ml dioxane. After the addition was complete the solution was stirred at room temp. and then at 60 C. to ensure complete reaction of the BH3'e2. The solution contained a little white precipitate. [00241] The catalyst was activated prior to use by heating 1500 mg of PdCl2[dppf].CH2Cl2 with 30 ml of triethylamine in 370 ml dioxane at 80 C. from for 7.5 h. 67 ml of this dark brown solution was used in the reaction. [C00065] [00242] To the pinacolborane solution was added 120 ml (863 mmol) dry triethylamine, 92 g (352.5 mmol) p-iodoacetanilide and then 67 ml of the catalyst solution. The reaction solution was placed in the oil bath at 80 C. The solution became clear and pale brown in colour and after about 1 to 2 h, a precipitate of the amine.HI salt separated. After 5 h the reaction was over 90percent complete. Heating was continued for several more hours after which no starting material was observed, by gc, to be in the reaction solution. The reaction product in a number of such reactions was always over 90percent by gc, the only side product observed was acetanilide. No phenylboronic acid pinacol ester were seen in the gc unless very strong solutions were employed. [00243] The crude product was isolated by removing the amine salt from the solution at room temp. The excess pinacolborane was destroyed with dry methanol. After reducing the volume of the reaction solution, the product was precipitated with petroleum ether. The dark coloured impurity in the product was removed by passing a solution of the product in toluene through a short column of Merck type 9385.1000 silica gel 60. The product was obtained as a white solid, mp>162 C. from toluene. [00244] The presence of borane methyl sulfide complex in these reactions does not stop the reaction from progressing. It can retard rate of the reaction somewhat but indications are that it can retard, especially with certain substrate, the dehalogenation reaction to a greater extent than the boronation reaction and so lead to an increase in product yield.

Molecular Weight:261.13
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:261.1536237
Monoisotopic Mass:261.1536237
Topological Polar Surface Area:47.6
Heavy Atom Count:19
Complexity:333
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes