tert-butyl 5-bromo-3-hydroxypyridin-2-ylcarbamate

The preparation of 5-bromo-3-hydroxy-2-tert-butyloxycarbonylamino pyridine (0038) To a solution of 2-amino-3-hydroxy-5-bromopyridine (10.0 g, 53.0 mmol) and EtGeneral procedure: 0.55 g (4 mmol) of potassium carbonate, 0.43 g (1.5 mmol) of compound (20) was dissolved and dispersed in 20 mL of DMF, and 0.395 g (1.0 mmol) of intermediate (19) or (19R) was added dropwise at 20 C under nitrogen atmosphere. The DMF solution was added and heated to 40 C for about 4 h. Then, the reaction solution was diluted with DCM, slowly poured into ice water and quenched, extracted with DCM, washed with saturated aqueous sodium chloride for 5 times, dried over anhydrous sodium sulfate, and the yield was between 15-30%.Example 8 The preparation of 5-bromo-3-(1-(2, 6-dichloro-3-fluorophenyl)ethoxy)-2-tert-butyloxycarbonylamino pyridine (0048) 1-(2, 6-dichloro-3-fluorophenyl)ethanol (1.0 g, 4.78 mmol), 5-bromo-3-hydroxy-2-tert-butyloxycarbonyl amino pyridine (1.4 g, 4.78 mmol) and triphenylphosphine (1.6 g, 6.2 mmol) were dissolved in 20 ml of anhydrous THF under N2atmosphere, cooled to below 0 C. and then diisopropylazodiformate (1.08 g, 6.2 mmol) was added to the mixture at below 5 C. The mixture was stirred at room temperature for 6 h, and then was allowed to filtrate. The solvent was removed under reduced pressure to afford product as oil which was recrystallized by ethanol to produce 2.14 g of 5-bromo-3-(1-(2, 6-dichloro-3-fluorophenyl)ethoxy)-2-tert-butyloxy carbonylamino pyridine as a white solid with a yield of 93.3%.Example 5 The preparation of (R)-5-bromo-3-(1-(2, 6-dichloro-3-fluorophenyl)ethoxy)-2-tert-butyloxycarbonylamino-pyridine (0045) (S)-1-(2, 6-dichloro-3-fluorophenyl)ethanol (1.0 g, 4.78 mmol, ee 99.9%), 5-bromo-3-bromo-3-hydroxyl-tert-butyloxycarbonylamino pyridine (1.4 g, 4.78 mmol) and triphenylphosphine (1.6 g, 6.2 mmol) were dissolved in 20 ml of anhydrous THF under N2atmosphere, cooled to below 0 C. and then diisopropylazodiformate (1.25 g, 6.2 mmol) was added to the mixture at below 5 C. The mixture was stirred at room temperature for 6 h and then filtered. The solvent was evaporated under reduced pressure to afford product as oil which was recrystallized by ethanol to produce 2.16 g of 5-bromo-3-(1-(2, 6-dichloro-3-fluorophenyl)ethoxy)-2-tert-butyloxycarbonylamino pyridine as a white solid with a yield of 94.3%, ee 99.9%.The preparation of 5-bromo-3-hydroxy-2-tert-butyloxycarbonylamino pyridine (0038) To a solution of 2-amino-3-hydroxy-5-bromopyridine (10.0 g, 53.0 mmol) and Et3N (10 mL, 71.8 mmol) in dichloromethane (100 mL) was added Boc2O (12.7 g, 58.4 mmol). The mixture was stirred at room temperature for 18 h and continued to stir for 30 min after the addition of 150 ml water. The reaction mixture was filtrated off through celite. The organic layer was separated and the aqueous layer was extracted with 150 dichloromethane. The combined organic layers were washed with saturated NaCl aqueous solution (2×100 mL) and then dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the obtained residue was triturated in hexane (100 mL), filtrated, and dried under vacuum to afford 15.0 g 5-bromo-3-hydroxy-2-tert-butyloxycarbonylamino pyridine as a white solid, with a yield of 98.0percent. (0039) 1H NMR (400 MHz, CDCl3): delta 7.98 (d, J=2.0 Hz, 1H), 7.58 (d, J=2.0 Hz, 1H), 4.67 (brs, 2H), 1.56 (s, 9H); 1C NMR (100 MHz, CDCl3): delta 150.4, 150.1, 145.3, 133.5, 131.5, 106.5, 85.0, 27.6.

Molecular Weight:289.13
XLogP3:2.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:288.01095
Monoisotopic Mass:288.01095
Topological Polar Surface Area:71.4
Heavy Atom Count:16
Complexity:255
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes