Preparation background and overview of 4-pentyloxybiphenylboronic acid
4-Pentoxybiphenylboronic acid can be used as a pharmaceutical synthesis intermediate, such as for the preparation of anidulafungin, which is a derivative of amphotericin B. This drug is manufactured by Vicuron Pharmaceuticals in the United States. The third-generation semi-synthetic antifungal drug developed by the company is called Eraxis and was approved for marketing in the United States in 2006. Compared with other echinocin antifungals, anidulafungin has a larger volume of distribution and broader spectrum of antibacterial activity.
Preparation of 4-pentyloxybiphenylboronic acid
Preparation of 4-pentyloxybiphenylboronic acid 1) Synthesis of sodium carbonate 4’-bromo-4-n-pentyloxybiphenyl
Add 1450mL water and 21.2g sodium hydroxide into a 2L three-necked flask, stir and dissolve, add 120g 4-hydroxy-4′-bromobiphenyl and 6g tetrabutylammonium bromide, stir at room temperature for 10 minutes and then drop Add 87.2g of 1-bromopentane, and reflux for 5 hours after the dropwise addition. After the reaction reaches room temperature, it is suction-filtered. The filter cake is washed with mL of water. The resulting solid is hot-beaten with 600 mL of n-heptane/water (1:1) mixed solution. , suction filtration and washing the filter cake with 60 mL n-heptane. The solid obtained was vacuum dried at 60°C for 5 hours, and the yield was 87%. 1HNMR (d6 DMSO, MHz) δ8.04-8.02 (m, 2H), 7.85-7.83 (m, 1H), 7.63-7.57 (m, 3H), 7.02-7.00 (m, 2H), 4.01-3.98 (m, 2H), 1.75 (t, J=8.0Hz, 2H), 1.41-1.36 (m, 4H), 0.92-0.89 (m, 3H).
Preparation of 4-pentyloxybiphenylboronic acid 2) Synthesis of 4-pentyloxybiphenylboronic acid
Under nitrogen protection, add 5g 4′-bromo-4-n-pentoxybiphenyl, 88mg palladium acetate, 4.6g potassium acetate, 144mg tris(o-methylphenyl)phosphine and 15mL tetrahydrofuran into a 100mL three-necked flask. , cool the calcium carbonate to 0-10°C in an ice water bath, dissolve 1.84g tetrahydroxydiboron in 10mL methanol and add it dropwise to the reaction. Stir the reaction at room temperature. After the raw materials disappear, add 30mL ethanol to dilute, filter, and use 10mL for the filter cake. Wash with ethanol, spin the filtrate to dryness, add 80 mL of methylene chloride/water mixed solvent (1:1), and heat and beat at 40°C for 1 hour. Cool to room temperature and then filter with suction. The filter cake is washed with 5 mL of water and 5 mL of methylene chloride in sequence, 50 After vacuum drying at ℃, 2.84g of white solid 4-pentoxybiphenylboronic acid was obtained, with a yield of 64%. 1HNMR (d6 DMSO, MHz) δ7.98-7.96 (m, 2H), 7.85-7.83 (m, 2H), 7.62-7.57 (m, 4H), 7.02-7.00 (m, 2H), 4.02 (t, J=6.0Hz, 2H), 1.73-1.72 (m, 2H), 1.39-1.37 (m, 4H), 0.92 (t, J=6.0Hz, 3H).
References
[1] CN201811401127.9 Preparation method of anidulafungin side chain intermediate p-pentoxyterbenzoic acid
