2-methoxy-4-[(methylsulfonyl)methyl]benzenamine synthesis

Yield:895636-32-5 83%

Reaction Conditions:

Stage #1: 4-(chloromethyl)-2-methoxy-1-nitrobenzene;sodium methansulfinate in ethanol at 80; for 16 h;
Stage #2: with hydrogen;palladium 10% on activated carbon in ethanol at 20; under 2585.81 Torr;

Steps:

B84.B

Step B/lntermediate B84: 2-(methyloxy)-4-[(methylsulfonyl)methyl]aniline; To a solution of 3-methoxy-4-nitrobenzyl chloride (2.76 g, 13.7 mmol) in 20 mL of absolute ethanol was added methanesulphinic acid sodium salt (1.0 g, 27.4 mmol). The reaction was heated to 80⁰C for 16h. The reaction was cooled to room temperature and poured into water and the aqueous layer was extracted with ethyl acetate. Combined organics were dried over anhydrous MgSO₄, filtered, concentrated onto silica gel and purified by flash chromatography with ethyl acetate/hexanes as the eluent. The fractions containing the desired product were concentrated to dryness, then redisolved in absolute ethanol and 10% Palladium on carbon (500 mg) was added and the reaction was placed on the Fischer-Porter hydrogenation apparatus and treated with 50 psi of H₂ gas overnight to afford 2- (methyloxy)-4-[(methylsulfonyl) methyl]aniline (2.46g, 83%). ¹H NMR (400 MHz, CDCI₃) δ ppm 6.80 (d, J = 1.7 Hz, 1 H), 6.68 (d, J = 8.0, 1.6 Hz, 1 H), 6.57 (d, J = 8.1 , 1 H), 4.82 (s, 2H), 4.21 (s, 2H), 3.72 (s, 3H).

References:

WO2009/20990,2009,A1 Location in patent:Page/Page column 122-123