Background and overview of the preparation method of 3-amino-5-hydroxypyridine
3-Amino-5-hydroxypyridine is a pyridine organic compound that can be used as an intermediate in organic synthesis.
Preparation method and structure of 3-amino-5-hydroxypyridine
Preparation method of 3-amino-5-hydroxypyridine Preparation method
The preparation of 3-amino-5-hydroxypyridine is divided into the following steps:
Step 1: 3-benzyloxy-5-bromopyridine
Cool NaH (60% in mineral oil) (40.9g, 1.0225mol) in 800mL DMF to 0°C and add benzyl alcohol (105mL, 1.014mol) slowly. The reaction mixture was stirred at 20 °C for 1 h, then 3,5-dibromopyridine (200.4 g, 846 mmol) was added and the mixture was stirred for 16 h. The mixture was quenched with saturated NHCl (500 mL), diluted with mL water, and extracted with Et2O (5 × 300 mL). The combined Et2O extracts were washed with 50% brine (6 x 300 mL) and dried (MgSO4). The solvent was evaporated in vacuo and the crude product was recrystallized from Et2O to give 161 g (72%) of the title product, m.p. 63-68°C. 1 H NMR (CDCl3, 300MHz) δ 8.37-8.27Cm, 2H), 7.5-7.35 (m, 6H), 5.1 (s, 1H). MS (DCI/NH3) m z 264, 266 (M+H)+.
Step 2: 3-amino-5-benzyloxypyridine
Combine 3-benzyloxy-5-bromopyridine (41.3g, 156mmol), copper(I) bromide (22.43g, 156mmol), MeOH (275mL) and liquid NH3 (50mL) in a stainless steel reactor , and heated to 130°C. 24 hours. The mixture was cooled to ambient temperature and concentrated. The residue was suspended in 300 mL of saturated aqueous Na2CO3 solution and extracted with CH2Cl2 (4 x 500 mL of pyridone). The combined CH2Cl2 extracts were washed with brine, dried (MgSO4) and concentrated. Crude oil products are
Chromatographic separation (silica gel; hexane/EtOAc, 9:1 to 7:3) yielded 15.6 g (50%) of the tidal compound. 1 H NMR (CDCl 3, 300 MHz) δ 8.21-8.29 (m, 2H), 7.44-1.26 (m, 6H), 5.10 (s, 2H). MS(DCI/NH3)m/z 201(M+H)+.
Step 3: 3-amino-5-hydroxypyridine
A solution of 3-amino-5-benzyloxypyridine (15.47 g, 77.25 mmol) in MeOH (25 mL) was stirred for 48 h in the presence of 5% Pd/C (100 mg) calcium carbonate under a H2 atmosphere. The mixture was filtered and concentrated, and the crude product was chromatographed (silica gel; CHCl/MeOH, 9:1) to give 4.5 g (53%) of the title compound MS (DCI/NH) m/z 111 (M+)H )+, 128(M + NH4)+. 1H NMR (CDCl 3, 300MHz) δ 7.4 (d, J = 3Hz, 1H), 7.3 (d, J = 2.5Hz, 1H), 6.33 (dd, J = 2.6Hz, 1H).
