1-MethoxyMethoxy-3-nitro-benzene synthesis

Yield:25458-48-4 93.6%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in dichloromethane at 0 - 20; for 3 h;

Steps:

131

EXAMPLE 131; 4-Amino-3-{3-[3-(2-morpholin-4-yl-ethoxy)-benzoylamino]-phenoxymethyl}-thieno[3,2-c]pyridine-7-carboxylic acid (2-hydroxy-ethyl)-amide; N,N-Diisopropylethylamine (15.51 g, 120 mmol) (Aldrich) was added to a suspension of 3-nitrophenol (13.91 g, 100 mmol) (Aldrich) in dichloromethane (50 mL) with cooling in an ice-water bath. Chloromethylmethyl ether (15.19 mL, 200 mmol) (Aldrich) was then added dropwise and the mixture stirred at room temperature for 3 hours. The mixture was then washed with mixture of brine (30 mL) and water (30 mL), followed by 0.1 N HCl (3×20 mL) and brine (2×20 mL). Aqueous layers were back washed with dichloromethane (30 mL). Organic solutions were combined, dried (MgSO₄), filtered and concentrated. Residue was filtered through silica gel (Biotage 40M) eluting with dichloromethane. Fractions were combined and concentrated to give methoxymethoxy-3-nitro-benzene as pale yellow oil. (Yield 17.15 g, 93.6%).

References:

US2007/60607,2007,A1 Location in patent:Page/Page column 60