F Isovaleraldehyde

Isopropylacrylaldehyde oxime, 2453 f Isopropyl vinyl ether, 1957 f Isovaleraldehyde, 1958 Limonene, 3337... 

Isosorbide mononitrate, see 1,4,3,6-Dianhydroglucitol 2-nitrate, 2390 3-Isothiocyanatopropene, see Allyl isothiocyanate, 1467 f Isovaleraldehyde, 1952 f Isoxazole, 1107... 

The optically active 1,3-/ram-substitutcd tetrahydro-/f-carboline 3 is obtained predominantly on treatment of the imine 2, derived from L-tryptophan and isovaleraldehyde, with A-benzyl -oxycarbonyl-L-prolyl chloride145. 

The P-cyanodiester 4 was prepared by condensation of isovaleraldehyde with diethyl malonate followed by the addihon of potassium cyanide. The cyanodiester 4 was hydrolyzed and decarboxylated to give the P-cyano acid 5. Reduction with Raney nickel gave racemic pregabalin (6), which was resolved with (S)-mandelic acid. The diastereomeric salt was split with wet TH F under neutral conditions to give pregabalin, which was recrystallized from isopropanol (IPA) to give the final Active Pharmaceutical Ingredient (API). 

ISOVALERALDEHYDE (107-83-5) Forms explosive mixture with air (flash point —20°F/—9°C). Violent reaction with strong oxidizers. Incompatible with nitric acid, sulfuric acid. Flow or agitation of substance may generate electrostatic charges due to low conductivity. 

Acetylphloroglucinol monomethyl ether heated 12 hrs. at 170-175° with 3-hydroxy-isovaleraldehyde dimethyl acetal and pyridine -> chromene deriv. Y 68%. F. e., also from aldehydes in place of acetals, s. W. M. Bandaranayake, L. Crombie, and D. A. Whiting, Chem. Commun. 1969, 970 cf. H. P. S. Chawla, P. K. Grover, and N. Anand, Indian. J. Chem. 8, 472 (1970). 

Chan, F., G.A. Reineccins, Reaction kinetics for the formation of isovaleraldehyde, 2-acetyl-1-pyrroline, di(H)di(OH)-6-methylpyranone, phenylacetaldehyde, 5-methyl-2-phenyl-2-hexenal, and 2-acetylfuran in model systems, in Maillard Reactions in Chemistry, Food, and Health, T.P. Labuza, G.A. Reineccius, V. Monnier, J.O. O Brien, J.W. Baines, Eds., Royal Chem. Soc. London, London, 1994, p. 131. 

Piperidine and pyridine added at room temp, to a stirred soln. of 4-hydroxy-6-methyl-2-pyridone in methanol-ethanol, after 5 min. isovaleraldehyde added drop-wise during 3 min., and refluxed 16 hrs. product. Y 80%. F. e. s. J. A. Findlay et al.. Can. J. Chem. 54, 270 (1976). 

Isoamyl bromide added slowly to a soln. of 2.5 moles of trimethylamine oxide in chloroform with stirring and initial warming to start the reaction, finally refluxed 30 min. isovaleraldehyde. Y 66%,—This simple one-step process is particularly suited for the prepn. of aliphatic aldehydes. F. e., also from tosylates, s. V. Franzen and S. Otto, B,94, 1360 (1961). 

---