1-Hydroxy-6-iodonaphthalene synthesis

Yield:-

Reaction Conditions:

Stage #1: 6-aminonaphthalen-1-olwith hydrogenchloride;sodium nitrite in water at 0; for 1 h;
Stage #2: with potassium iodide in water at 20; for 4 h;

Steps:

9 Example 9; Synthesis of methyl 3-[4-cyclopentylmethyloxy-3-(5-hydroxynaphthalen-2-yl)Phenyl]-propionate (Compound No. 009) (Preparation Method 4, Step d-1)

Example 9 Synthesis of methyl 3-[4-cyclopentylmethyloxy-3-(5-hydroxynaphthalen-2-yl)Phenyl]-propionate (Compound No. 009) (Preparation Method 4, Step d-1) 2-Amino-5-hydroxynaphthalene (4.80 g, TCI) was dissolved in 6 N hydrochloric acid (300 ml), added dropwise with an aqueous solution (22.5 ml) of sodium nitrite (2.25 g, WAKO) under ice cooling over 30 minutes and stirred for 30 minutes.The reaction mixture was added dropwise with an aqueous solution (75 ml) of potassium iodide (9.90 g, WAKO), stirred for 30 minutes, then warmed to room temperature and further stirred for 3.5 hours.The reaction mixture was neutralized with aqueous ammonia and then filtered by using Celite. The filtrate was added with ethyl acetate (90 ml*2) for extraction.The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate, saturated aqueous ammonium chloride and saturated brine and dried, and then the solvent was evaporated under reduced pressure.The residue was purified by column chromatography (Quad, hexane:ethyl acetate=10:1) to obtain 1-hydroxy-6-iodonaphthalene (1.48 g).A solution of this compound (539 mg) in anhydrous THF (10 ml) was added with 60% sodium hydride (171 mg) under ice cooling and stirred for 1 hour.The reaction mixture was cooled to -78° C. under argon atmosphere, added dropwise with 1.6 M solution of n-butyllithium in hexane (3.75 ml, Aid) over 10 minutes and stirred for 30 minutes.This reaction mixture was added dropwise with (IPrO)3B (1.16 ml) over 10 minutes, stirred for 30 minutes, then warmed to room temperature and further stirred for 3 hours.The reaction mixture was added with water (3 ml) and 0.5 M aqueous sulfuric acid (7 ml) and extracted with diethyl ether (100 ml*3).The organic layer was washed with saturated brine and dried, and then the solvent was evaporated under reduced pressure to obtain crude 7-hydroxy-2-naphthaleneboronic acid.According to the procedure described in the synthesis method of Compound of Example 001 (Preparation Method 4, Step d-1) with the modifications that the reaction was carried out for 14 hours, and the purification was performed by column chromatography (Quad, hexane:ethyl acetate=6:1), a solution of the above compound in ethanol (1 ml), Intermediate 3 (350 mg), 2 M aqueous sodium carbonate (2.4 ml) and (Ph3P)4Pd (116 mg) were reacted and treated to obtain the title compound (Compound No. 009, 388 mg).

References:

US2004/44258,2004,A1 Location in patent:Page 61-62