2-Chloro-N-[2-chloro-6-(hydroxyMethyl)phenyl]-acetaMide synthesis

Yield:910297-66-4 85%

Reaction Conditions:

Stage #1: 3-chloro-2-(2-chloroacetamido)benzyl 2-chloroacetatewith methanol;lithium hydroxide;water in tetrahydrofuran at -10 - 15; for 4 h;
Stage #2: with water;ammonium chloride in tetrahydrofuran;

Steps:

1.C

C. Preparation of compound 2-chloro-N-(2-chloro-6-(hydroxymethyl)phenyl)acetamide (5a); Lithium hydroxide mono hydrate (12.55 g, 306 mmol) was dissolved in H₂O (50 mL). To the solution was added MeOH (50 mL). The mixture was then cooled to -10° C. A solution of compound 4a (19.0 g, 61.2 mL) in THF (300 mL) was added. The reaction mixture was allowed to warm to 15° C. over a period of 4 h. A saturated NH₄Cl solution (200 mL) and EtOAc (200 mL) were added. The organic phase was separated and the aqueous layer was extracted with EtOAc (200 mL). The combined organic extracts were washed with brine (2×200 mL), dried over Na₂SO₄, filtered and concentrated in vacuo to give the crude compound 4 which was crystallized from a mixture of EtOAc and hexane (1:4) to give the pure compound 5a as a off white needles (12.1 g, 85% yield). ¹H NMR (500 MHz, CDCl₃) δ 2.96 (bs, 1H), 4.29 (s, 2H), 4.56 (s, 2H), 7.30 (t, J=5.0 Hz, 1H), 7.44 (t, J=5.0 Hz, 2H), 8.33 (bs, 1H); Anal. Calcd for C₉H₉Cl₂NO₂: C, 46.18; H, 3.87; N, 5.98. Found: C, 46.21; H, 3.72; N, 5.80.

References:

US2006/211705,2006,A1 Location in patent:Page/Page column 33-34