Sulfuric Acid → Isopropylacetate iso-octane

関与物質

反応手順

Suitable reaction conditions are: 2-(4-cyanophenoxy)-2-methylpropionic acid (or compound (viii)) (1 wt) was dissolved in methanol and trimethylorthoformate (TMOF, 1 vol) with stirring under nitrogen1. Sulfuric acid (98%, 0.08 vol, 0.32 eq) was then added, and the mixture was heated to reflux with HPLC monitoring. The reaction was typically complete after approx 1.5-2 hrs at reflux. The batch was cooled, and added to a stirred suspension of potassium carbonate (0.65 eq) in isopropyl acetate and then concentrated in vacuo to a total volume of approx 4 vol. Isopropyl acetate was added, and the slurry concentrated in vacuo to a total volume of approx 4 vol. Isopropyl acetate (4 vol) and water (5 vol) was added, the resultant biphasic solution was separated, and the organics were washed with water. The product was obtained by crystallisation from isopropylacetate/iso-octane with seeding. Expected yield: 93% theory, 99% w/w. Suitable reaction conditions for compound of formula (II) where X is H are: The compound (vii) is suspended in IMS containing AcOH, and treated with 10% Pd/C catalyst (50% wet, 0.1 wt). Hydrogenated at room temp for 60-90 mins until essentially complete by HPLC. The aminoacid precipitates during the reduction to give a fairly thick slurry at the end of the reaction. This is diluted with water and heated to obtain a complete solution. Filtered through celite to remove catalyst and washed through with 1:1 aq IMS. The filtrate and washings are concentrated in vacuo to ca 10 vols, and treated with cHCl (1 vol). Reconcentrated in vacuo to ca 4 vols, by which time a thick slurry results. This is collected by vacuum filtration and washed with water and dried at 50C in vacuo to constant weight. Yield is 70-75% as hydrochloride salt.

情報源と証拠