2-BROMO-1-NITRO-4-PHENOXYBENZENE synthesis

Yield:1258545-24-2 94%

Reaction Conditions:

Stage #1: phenolwith caesium carbonate in acetonitrile at 20; for 0.166667 h;
Stage #2: 2-bromo-4-fluoronitrobenzene in acetonitrile at 50; for 65 h;

Steps:

71

Example 71; Synthesis of (3S)-3-amino-1-hydroxy-6-phenoxy-3,4-dihydroquinolin-2(1H)-one, hydrochloride salt (93); 2-Bromo-1-nitro-4-phenoxybenzene (90); Phenol (11.1 g, 118 mmol) was added to a suspension of Cs₂CO₃ (46.2 g, 142 mmol) in MeCN (295 mL). The resulting solution was stirred at RT for 10 min, then 2-bromo-4-fluoronitrobenzene (26.0 g, 118 mmol) was added, and the reaction mixture was heated to 50° C. for 65 h. The reaction mixture was cooled to RT and filtered to remove Cs₂CO₃. The filtrate was concentrated in vacuo, and the resulting residue was dissolved in EtOAc (150 mL) and washed with aqueous sodium hydroxide solution (1 N, 250 mL), water (2×250 mL), and saturated aqueous sodium chloride solution (250 mL). The separated organic phase was dried over Na₂SO₄, filtered, and concentrated in vacuo. Purification by silica gel chromatography (Eluant: heptane) provided the title compound as a pale yellow oil (32.7 g, 94%). ¹H NMR (400 MHz, CDCl₃) δ 6.97 (dd, J=9.1, 2.6 Hz, 1H), 7.08-7.12 (m, 2H), 7.26-7.31 (m, 2H), 7.43-7.49 (m, 2H), 7.95 (d, J=9.1 Hz, 1H).

References:

US2010/324043,2010,A1 Location in patent:Page/Page column 44