Related Products of 7073-69-0, With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.7073-69-0, name is 2-(2-Bromophenyl)propan-2-ol, molecular formula is C9H11BrO, molecular weight is 215.087, as common compound, the synthetic route is as follows.
To a mixture of methyl 2-bromobenzoate (20 g, 93.00 mmol, 13.07 mL, 1 eq) in THF (200 mL) was added dropwise MeMgBr (3 M, 65.10 mL, 2.1 eq) at 5C under N2. The mixture was stirred at 25C for 2 h and then quenched with aqueous NH4CI (200 mL). The aqueous phase was extracted with ethyl acetate (100 mL x 3). The combined organic phase was washed with brine (150 mL), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by flash silica gel chromatography (ISCO; 120 g SepaFlash Silica Flash Column, Eluent of 0- 30% Ethyl acetate/Petroleum ethergradient, 80 mL/min) to afford 2-(2- bromophenyl)propan-2-ol (13 g, 60.44 mmol, 64.99% yield) as light-yellow oil. 1H NMR (CDCIs, 400 MHz): d 7.67 (d, J = 7.6 Hz, 1 H), 7.59 (d, J = 7.6 Hz, 1 H), 7.31 (t, J = 7.6 Hz, 1 H), 7.12 (t, = 7.6 Hz, 1 H), 1.77 (s, 6H) ppm. To a mixture of 2-(2- bromophenyl)propan-2-ol (12 g, 55.79 mmol, 1 eq) in THF (120 ml_) was added n- BuLi (2.5 M, 55.79 ml_, 2.5 eq) in one portion at -70C. The mixture was stirred at – 70C for 2 h. Then triisopropyl borate (20.99 g, 111.58 mmol, 25.65 ml_, 2 eq) was added to the mixture. The mixture was warmed to 20C and stirred for 15 h. The residue was poured into ice-water (w/w = 1/1) (10 ml_) and adjust to pH 5. The aqueous phase was extracted with ethyl acetate (10 mL x 3). The combined organic phase was washed with brine (15 mL), dried with anhydrous Na2S04, filtered and concentrated in vacuum. The residue was purified by flash silica gel chromatography (ISCO; 80 g SepaFlash Silica Flash Column, Eluent of 0-100% Ethyl (0480) acetate/Petroleum ethergradient, 100 mL/min) to afford 3,3-dimethylbenzo (0481) [c][1 ,2]oxaborol-1 (3H)-ol (9 g, 55.56 mmol, 99.6% yield) as crude yellow oil. 1H NMR (CDCIs, 400 MHz): d 9.00 (s, 1 H), 7.67 (d, J = 7.2 Hz, 1 H), 7.47-7.41 (m, 2H), 7.33- 7.31 (m, 1 H), 1.45 (s, 6H) ppm. To a mixture of 3,3-dimethylbenzo[c][1 ,2]oxaborol- 1 (3H)-ol (9 g, 55.56 mmol, 1 eq) in H2S04 (100 mL) was added HNOs (10.50 g, 166.67 mmol, 7.50 mL, 3 eq) at -20C. The mixture was stirred at -15C for 10 min. Ice-water (100 mL) was added to the mixture at -10C and stirred for 10 min. It was filtered and then the solid was washed by petroleum ether (50 mL) to afford crude 3,3-dimethyl-6-nitrobenzo[c][1 ,2]oxaborol-1 (3H)-ol (8 g, 38.65 mmol, 69.6% yield) as yellow solid. 150 mg of crude product was purified by pre-HPLC (column: Xtimate C18 150*25mm*5um; mobile phase: [water (10mM NH4HC03)-ACN]; B%: 10%-40%, 10.5 min) to afford the purified material of 3,3-dimethyl-6-nitrobenzo[c][1 ,2]oxaborol- 1 (3H)-ol (91 mg) as yellow solid. 1H NMR (DMSO-cfe, 400 MHz): d 9.47 (s, 1 H), 8.52 (d, J = 2.4 Hz, 1 H), 8.32 (dd, J = 8.4, 2.4 Hz, 1 H), 7.73 (d, J = 8.4 Hz, 1 H), 1.49 (s, 6H) ppm. MS (ESI): mass calcd. For C9HI0BNO4 207.07, m/z found 206.1 [M-H] HPLC purity: 100% (220 nm) and 100% (254 nm). To a solution of 3,3-dimethyl-6- nitrobenzo[c][1 ,2]oxaborol-1 (3H)-ol (2 g, 9.66 mmol, 1 eq) in EtOAc (70 mL) was added Pd/C (0.5 g, 10% purity) under N2. The suspension was degassed under vacuum and purged with H2 several times. The mixture was stirred under H2 (15 psi) at 20C for 15 h. The reaction mixture was filtered, and the filtrate was concentrated to affrord 6-amino-3,3-dimethylbenzo[c][1 ,2] oxaborol-1 (3H)-ol (1.5 g, 8.47 mmol, 87.70% yield) as red solid. 100 mg of the crude product was purified by pre-HPLC (column: Xtimate C18 150*25mm*5um; mobile phase: [water (10mM NH4HC03)- ACN]; B%: 10%-40%, 10.5 min) to afford 6-amino-3,3-dimethylbenzo[c][1 ,2]oxaborol- 1 (3H)-ol (51 mg) as yellow solid. 1H NMR (DMSO-cfe, 400 MHz): d 8.73 (s, 1 H), 7.02 (d, J = 8.0 Hz, 1 H), 6.79 (d, J = 2.0 Hz, 1 H), 6.67 (dd, J = 8.0, 2.4 Hz, 1 H), 4.95 (s, 2H), 1.37 (s, 6H) ppm. MS (ESI): mass calcd. For C9Hi2BN02 177.10, m/z found 176.1 [M-H]-. HPLC: 99.4% (220 nm), 98.6% (254 nm). To a mixture of 6-amino-3,3- dimethylbenzo[c][1 ,2]oxaborol-1 (3H)-ol (1 g, 5.65 mmol, 1 eq) in t-BuOH (20 mL) was added (Boc)20 (3.70 g, 16.95 mmol, 3.89 mL, 3 eq) in one portion at 20C under N2. The mixture was stirred at 50C for 12 h and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO; 12 g SepaFlash Silica Flash Column, Eluent of 0-80% Ethyl acetate/Petroleum ethergradient: 30 mL/min) to afford tert-butyl (1-hydroxy-3,3-dimethyl-1 ,3-dihydrobenzo[c][1 ,2]oxaborol- 6- yl)carbamate (0.6 g, 2.17 mmol, 38.32% yield) as yellow oil. 1H NMR (CDCh, 400 MHz): d 7.60 (s, 1 H), 7.54 (d, J = 8.0 Hz, 1 H), 7.21 (d, J = 8.0 Hz, 1 H), 6.53 (s, 1 H), 1.55 (s, 9H), 1.54 (s, 6H). To a mixture of tert-butyl (1 -hydroxy-3, 3-dimethyl-1 , 3- dihydrobenzo[c][1 ,2]oxaborol-6-yl)carbamate (0.5 g, 1.80 mmol, 1 eq) in DMF (10 mL) was added NCS (240.93 mg, 1.80 mmol, 1 eq) in one portions at 0C. The mixture was stirred at 50C for 15 h and then poured into water (10 mL). The aqueous phase was extracted with ethyl acetate (10 mL x 3). The combined organic phase was washed with brine (10 mL),…
The chemical industry reduces the impact on the environment during synthesis 7073-69-0, I believe this compound will play a more active role in future production and life.
Reference:
Patent; BORAGEN, INC.; LIU, Chunliang; ZHANG, Yong-Kang; LIU, Chun, Yu; ZHOU, Yasheen; (372 pag.)WO2020/51575; (2020); A1;,
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