3-chloro-2-methoxyphenol synthesis

Yield: 62%

Reaction Conditions:

Stage #1:2,6-dichloroanisole with potassium hydroxide;tris-(dibenzylideneacetone)dipalladium⁽⁰⁾;tert-butyl XPhos in 1,4-dioxane;water at 100; for 2 h;
Stage #2: with hydrogenchloride in 1,4-dioxane;water

Steps:

22.A
Example 22; Part A; A reaction mixture of 1,3-dichloro-2-methoxybenzene (885 mg, 5 mmol), potassium hydroxide (280 mg, 5 mmol), tris(dibenzylideneacetone)dipalladium (115 mg, 0.125 mmol) and fe/f-butyl X-Phos (159 mg, 0.375 mmol) in dioxane/water (1 :1 , 5 ml_) was stirred at 100 ⁰C for 2 hours. The reaction mixture was mixed with aqueous hydrochloride solution (1 N). The organic components were extracted with EtOAc. The combined EtOAc layers were washed with brine, and then concentrated. The residue was purified by chromatography. Elution with 10% EtOAc in hexane gave 3-chloro-2- methoxyphenol (22-1 , 489 mg, 62% yield) as yellow oil. ¹H NMR (400 MHz, CDCI₃) δ 6.98-6.84 (m, 3H), 5.73 (br s, 1 H), 3.93 (s, 3H).

References:

SCHERING CORPORATION;SHIPPS, JR., Gerald, W.;CHENG, Cliff, C.;HUANG, Xiaohua;ACHAB, Abdelghani, Abe;ORTH, Peter;VOIGT, Johannes, H.;SOUCY, Kyle, Ann WO2010/56631, 2010, A1 Location in patent:Page/Page column 123