| 86.2% |
With sodium tetrahydroborate; In tetrahydrofuran; at 0 - 25℃; for 1.08333h; |
To a solution of (2-formylphenyl)boronic acid (10 g, 66.69 mmol, 1 eq) in THF (100 ml_) was added NaBH4 in portions (5.05 g, 133.39 mmol, 2 eq) at 0C over 5 min. After addition, the mixture was stirred at 25C for 1 hr. The reaction mixture was quenched by adding aq. HCI (2M) at 0C until pH to 7, and then diluted with EtOAc (30 ml_) and extracted with EtOAc (30 ml_ x 3). The combined organic layers were washed with brine (30 ml_ x 3), dried over Na2S04, filtered and concentrated under reduced pressure to give benzo[c][1 ,2]oxaborol-1 (3H)-ol (7.7 g, 57.49 mmol, 86.2% yield) as a white solid. 1H NMR (CDCI3, 400 MHz): d 7.78 (d, J = 7.2 Hz, 1 H), 7.53-7.49 (m, 1 H), 7.41-7.36 (m, 2 H), 5.75 (s, 1 H) and 5.15 (s, 2 H) ppm. To a solution of fuming HNO3 (70 ml_) was added benzo[c][1 ,2]oxaborol-1(3H)-ol (6.7 g, 50.02 mmol, 1 eq) at -30C over 5 min. After addition, the mixture was stirred at - 30C for 30 min. The reaction mixture was poured with stirring into water and ice (80 ml_) and stirred at 0C for 40 min. Solid was precipitated. The solid was filtered and dried under vacuum to afford 1-hydroxy-6-nitro-3H-2, 1-benzoxaborole (6 g, 33.53 mmol, 67.0% yield, 100% purity) as a pale yellow solid. 1H NMR (DMSO-cfe, 400 MHz): d 9.59 (s, 1 H), 8.57 (s, 1 H), 8.33 (dd, J = 8.4, 2.0 Hz, 1 H), 7.69 (d, J = 8.4 Hz, (0459) 1 H), 5.1 1 (s, 2 H) ppm. MS (ESI): mass calcd. For C7H8BN02 149.06, m/z found 150.1 [M+H]+. Purity by HPLC: 100% (220 nm) and 100% (254 nm). To a solution of 1-hydroxy-6-nitro-3H-2, 1-benzoxaborole (950 mg, 5.31 mmol, 1 eq) in EtOAc (20 ml_) was added Pd/C (200 mg, 10%) under N2. The suspension was degassed under vacuum and purged with H2 several times. The mixture was stirred under H2 (15 psi) at 25C for 2 hrs. The reaction mixture was filtered, and the filtrate was concentrated to give crude product. The crude product was purified by re-crystallization from 20 ml_ of MTBE to give 6-aminobenzo[c][1 ,2]oxaborol-1 (3H)-ol (0.73 g, 4.90 mmol, 92.3% yield, 100% purity) as a pale yellow solid. 1H NMR (DMSO-cfe, 400 MHz): d 8.90 (s, 1 H), 7.03 (d, J = 8.0 Hz, 1 H), 6.87 (s, 1 H), 6.69 (d, J = 8.0 Hz, 1 H), 4.97 (s, 2 H), 4.80 (s, 2 H) ppm. MS (ESI): mass calcd. For C7H8BN02 149.06, m/z found (0460) 150.1 [M+H]+. Purity by HPLC: 100% (220 nm) and 100% (254 nm). To a solution of 6-aminobenzo[c][1 ,2]oxaborol-1 (3H)-ol (1 g, 6.71 mmol, 1 eq) in DMF (15 mL) was added NCS (0.95 g, 7.11 mmol, 1.06 eq) at 0C. The mixture was stirred at 25C for 1.5 hr. The reaction mixture was quenched by adding ice-water (50 mL) at 0C, and then diluted and extracted with EtOAc (10 mL x 3). The combined organic layers were washed with brine (30 mL x 3), dried over Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by re (0461) crystallization from MTBE (20 mL) to afford crude product (800 mg, brown solid). (0462) Part of the crude product (270 mg, brown solid) was further purified by prep-TLC (Si02, Ethyl acetate/MeOH=10/1) to give 6-amino-7-chlorobenzo[c][1 ,2]oxaborol- 1 (3H)-ol (44.6 mg, 96.3% purity) was obtained as a yellow solid. 1H NMR (DMSO-cfe, 400 MHz): d 8.89 (s, 1 H), 7.03 (d, J = 8.0 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 5.21 (s, (0463) 2 H), 4.82 (s, 2 H) ppm. MS (ESI): mass calcd. For C7H7BCIN02 183.03, m/z found (0464) 184.2 [M+H]+. Purity by HPLC: 96.33% (220 nm). |
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