Phosphorus oxychloride → 2-(4-Bromophenyl)-4-(chloromethyl)-5-methyloxazole

Participants

Reaction Steps

A solution of 2-(4-bromophenyl)-4,5-dimethyl-oxazole-3-oxide (96.6 g, 0.36 mol) in CHCl3 (0.90 L) was treated dropwise with phosphorous oxychloride (61.1 g, 0.40 mol) allowing the reaction to exotherm and then stir at reflux for 30 min. The reaction was then cooled to rt and washed with water (2×1 L). The combined aqueous washes were back extracted with CH2Cl2 (2×400 mL). The organic layers were dried (MgSO4), and the solvent removed in vacuo to give crude product that was recrystallized from hot hexanes (300 mL), decanting the hot supernate away from a dark oily material. The remaining dark oil was agitated in additional hot hexanes (200 mL) and the combined supernates were cooled to 0° C. to crystallize the product which was isolated by filtration to give 74.2 g (72%) of 2-(4-bromophenyl)-4-(chloromethyl)-5-methyloxazole as a lime-green powder: Rf=0.39 in 20% EtOAc/hexanes; 1H NMR (500 MHz, CDCl3) δ 7.88-7.86 (m, 2H), 7.59-7.56 (m, 2H), 4.54 (s, 2H), 2.42 (s, 3H); 13C (125 MHz, CDCl3) δ 159.2, 146.9, 133.2, 132.0, 127.6, 126.1, 124.7, 37.1, 11.5; IR (KBr) 2970, 1633, 1599, 1481, 1401, 1258, 1117, 1008 cm−1; UV (EtOH) λmax 281 nm (ε 21349); HRMS (FAB) m/z calc'd for C11H1079BrClNO: 285.9634, found 285.9641; Anal. Calc'd for C11H9ClBrNO: C, 46.11; H, 3.17; N, 4.89; Cl, 12.37; Br, 27.88. Found C, 46.28; H, 3.07; N, 4.81; Cl, 12.36; Br, 27.88.

Provenance & Evidence