Sodium Nitrite → Ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)-4-methylpentanoate

Participants

Reaction Conditions

Reaction Steps

Ethyl 2-(3-amino-5-bromo-4-hydroxyphenyl)-4-methylpentanoate 1 (4 g, 0.012 mol) was dissolved in a mixture of ACN/H2O/HCl 60 mL/30 mL/8 mL at 0° C. A solution of NaNO2 (0.919 g, 1.1 eq) in water (10 mL) was added dropwise at 0° C. and the reaction mixture was stirred for 1 h at 0° C. A solution of CuCl (5.99 g, 0.060 mol) in water (10 mL) was added dropwise to the reaction mixture at 0° C. The reaction mixture was then heated to 50° C. for 2.5 h. upon which the mixture was poured into ice water, extracted with ethyl acetate (3×100 mL) The combined organic layers were washed with water (200 mL) and brine (100 mL), dried over NaSO4 and concentrated in vacuo to give crude black oil which was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)-4-methylpentanoate as yellow oil 2.2 g, (47.3%). 1H NMR (CDCl3, 200 MHz): 7.38 (s, 1H); 7.4 (s, 1H); 5.80 (bs, 1H); 4.13 (q, 2H); 3.51 (t, 1H); 1.93-1.56 (m, 2H); 1.51 (m, 1H); 1.21 (t, 3H), 0.97 (d, 6H);

Provenance & Evidence