(8-chloronaphthalen-1-yl)-(1-pentylindol-3-yl)methanone synthesis

Yield:1366067-88-0 33%

Reaction Conditions:

Stage #1: 1-pentyl-1H-indolewith dimethylaluminum chloride in hexane;dichloromethane at 0; for 1 h;Inert atmosphere;Friedel-Crafts reaction;
Stage #2: C₁₁H₆Cl₂O in hexane;dichloromethane at 0 - 20; for 6 h;Inert atmosphere;Friedel-Crafts reaction;

Steps:

5.1.1. 1-Propyl-3-(4-fluoro-1-naphthoyl)indole (JWH-414, 9, R = C₃H₇, R' = H, X = F)

General procedure: To a solution of 0.07 g (0.44 mmol) of 1-propylindole in 5 mL of dry dichloromethane under Ar was added 0.60 mL (0.60 mmol), of 1 M dimethylaluminum chloride in hexanes and the mixture was stirred for 30 min at 0 °C. To this mixture was added dropwise a solution of freshly prepared 4-fluoro-1-naphthoyl chloride in 3 mL of dry dichloromethane. The acid chloride was prepared by the addition of 3 mL (41 mmol) of thionyl chloride to 0.12 g (0.63 mmol) of 4-fluoro-1-naphthoic acid under Ar. The mixture was heated at reflux for 2 h, cooled to ambient temperature and the thionyl chloride was removed in vacuo. The acid chloride was added to the indole mixture without further purification and the mixture was stirred at ambient temperature overnight. The reaction was quenched with water and extracted with ether. The ethereal solution was washed with water and 1 M KOH, dried (MgSO₄) and the solvent was removed in vacuo to give the crude product, which was purified by column chromatography (petroleum ether/ether, 8:2) to give 0.076 g (52%) of 1-propyl-3-(4-fluoro-1-naphthoyl)indole as a tan solid

References:

Wiley, Jenny L.;Smith, Valerie J.;Chen, Jianhong;Martin, Billy R.;Huffman, John W. [Bioorganic and Medicinal Chemistry,2012,vol. 20,# 6,p. 2067 - 2081] Location in patent:experimental part