A-Naphthylacetic acid

Introduce a solution of 15 g. of the diazo ketone in 100 ml. of dioxan dropwise and with stirring into a mixture of 2 g. of silver oxide (1), 3 g. of sodium thiosulphate and 5 g. of anhydrous sodium carbonate in 200 ml. of water at 50-60°. When the addition is complete, continue the stirring for 1 hour and raise the temperature of the mixture gradually to 90-100°. Cool the reaction mixture, dilute with water and acidify with dilute nitric acid. Filter off the a-naphthylacetic acid which separates and recrys-talhse it from water. The yield is 12 g., m.p. 130°. 

Via the in situ activation, applying sulfonic acid chlorides, covalent binding of bioactive molecules onto dextran was achieved by esterification of the polymer with a-naphthylacetic acid (1), nicotinic acid (2) and naproxen (3) homogeneously in DMF/LiCl using p-toluenesulfonyl chloride (tosyl chloride, TosCl) or methanesulfonic acid chloride (mesyl chloride, MesCl) and pyridine within 22 h at 30-70 °C (Fig. 22). 

Table 8 Influence of the concentration of pyridine [Py], the reaction temperature, and type of sulfonic acid chloride applied for the esterification of dextran (0.12 mol L 1) in DMF/LiCl with a-naphthylacetic acid (0.37 mol L-1) for 22 h...

The nitrile is refluxed for 45 minutes with a mixture of 350 ml. of sulfuric acid and 350 ml. of water and then is poured into 3 1. of cold water with stirring. The precipitated acid is removed, dissolved in hot 50 ethanol-water mixture, and treated with activated carbon. The addition of water to the filtrate from the carbon treatment precipitates a-naphthylacetic acid melting at 131.5°. The yield of acid is 131.5 g, (56 based on chloromethylnaphthalene). 

Coinclusion of the aromatic guest and a small molecule, usually an aliphatic alcohol, in the cavity of a dextrin (i.e., the formation of a three-component complex) often enhances the emission. In this type of complex, the fluorophore is sandwiched between the CD wall and the alcohol, which acts as a spacer. More water molecules are expelled from the cavity and the fluorophore experiences an environment less polar than that experienced in the absence of a spacer. The phenomenon was first reported in reference 61 the enhanced fluorescence of a-naphthylacetic acid observed after addition of y-CD was further increased by addition of cyclohexanol. 

A team at Hoffmann-La Roche, in 2013, reported the application of this reaction as a key step in an efficient large-scale synthesis (about 3 kg) of a naphthylacetic acid CRTH2 receptor (involved in inflammation events, and thus important therapeutically for the treatment of asthma, allergic inflammation, COPD (chronic obstructive pulmonary disease), allergic rhinitis, and atopic dermatitis) antagonist, which is a naphthylacetic acid (Scheme 1.57) [180]. This whole process was scaled up to produce over 2 kg of the active pharmaceutical ingredient (API). 

Scheme 1.57 Negishi-Baba cross-coupling arylation step in the large-scale synthesis of a naphthylacetic acid CRTH2 receptor antagonist by Hoffmann-La Roche [180].

In 1941, Van Overbeck discovered that the fluid endosperm of the coconut, the coconut milk, can induce cell division in embryos grown in artificial culture media. Subsequently, Steward and his colleagues in particular investigated the influence of coconut milk on the growth of tissue cultures. They established a division-promoting effect of coconut milk in tissue cultures too. However, in most cases it was necessary to combine the coconut milk with a growth substance such as lAA, a-naphthylacetic acid or 2, 4-d if a strong and persistent capacity to divide was to be attained. 

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