1354727-98-2

Upstream product

• 5111-70-6 5-methoxy-1-indanone 
• 1354727-78-8 C₁₇H₁₆O 
• 1354727-89-1 C₁₇H₁₆O₃ 
• 1769-84-2 6-methoxy-2-phenyl-1-tetralone 

Downstream Products

• 1354728-06-5 C₁₇H₁₄O₂ 

Relevant academic research and scientific papers

Development of concise two-step catalytic approach towards lasofoxifene precursor nafoxidine

We have elaborated a two-step catalytic approach to nafoxidine, a key precursor to lasofoxifene. Firstly, an efficient α-arylation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one with chlorobenzene was developed, which operates at low 0.1 mol% Pd-132 catalyst loading in the presence of 1.9 equivalents of sodium tert-butoxide at 60 °C in 1,4-dioxane and provides 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one in 90% yield. Secondly, we have demonstrated that 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one can be converted to nafoxidine in 61% yield via CeCl3 promoted reaction with (4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)lithium, which is formed in-situ from the corresponding arylbromide precursor and n-butyllithium. Altogether, the shortest two-step approach to nafoxidine from simple tetralone commodity starting material has been developed with overall 55% yield. The developed synthetic approach to nafoxidine has several beneficial aspects over the one used in the synthetic route primarily developed for the preparation of lasofoxifene.

Synthesis of substituted α-tetralones and substituted 1-naphthols via regioselective ring expansion of 1-acyl-1-indanol skeleton

Substituted 1-acyl-1-indanols were prepared using the corresponding readily commercially available substituted indanones as starting materials. Treatment of each 1-acyl-1-indanol derivative with sodium methoxide in hot methanol furnished a regiospecific 2-hydroxy-α-tetralone derivative, which was an α-keto rearrangement product. Each substituted 2-hydroxy-α-tetralone then underwent dehydration to afford the corresponding 1-naphthol derivative.