Studies on the syntheses of analgesics. Part 50. Synthesis of optically active 2-[4-(1-oxo-2-isoindolinyl)phenyl]propanoic acid. [Studies on the syntheses of heterocyclic compounds. Part 742]

2-[4-(1-Oxo-2-isoindolinyl)phenyl]propanoic acid ( 1 ) having a potent analgesic and anti-inflammatory activity could be obtained by three methods, which were found to provide extremely useful ways for the synthesis of 1 from the industrial point of view. (E)- and (Z)-Isomers of 2-butenoic acid and oxiranecarboxylic acid derivatives as the intermedaites in the synthesis of 1 were separated and characterized. Furthermore, the optical resolution of (±)-2-[4-(1-oxo-2-isoindolinyl)phenyl]propanoic acid was successfully achieved using cinchonidine as a resolution reagent.     

Snytheses of analgesics. Part XXXVII. An alternative synthesis of 1,2,3,4, 5, 6-hexahydro-8-hydroxy-2,6-methano-6, h-dimethyl-3-phenethyl-3-benzazoeine [studies on the syntheses of heterocyclic compounds. Part DXXI]

Acid treatment of the alkylated products of (Va, Vb, and VIII) of piperidinols IVa and IVb, and tetrahydropyridine VII with β-bromoethylbenzene, afforded 1,2,3,4,5,6-hexahydro-8-hydroxy-2,6-methano-6,1 1-dimethyl-3-phenethyl-3-benzazocine (la) in good yield. Piperidinols Va and Vb were also obtained from the reaction of N-(3-methyl-3-pentenyl)-β-phenethylamine (IIb) with methyl 3-(4-methoxyphenyl)-2,3-epoxypropionate.     

Novel methylation. III. Methylation of tertiary amines such as pyridine and isoquinoline with alkyl carboxylates

The alkylation of tertiary amines, namely, 2-dimethylaminoethanol, triethylamine, pyridine and isoquinoline with various alkyl carboxylates was investigated. This reaction afforded the corresponding quarternary ammonium salts, e.g., methylation of 2-dimethyl-aminoethanol with methyl salicylate.     

Studies on the synthesis of chemotherapeutics. I. Synthesis of 1-(2-tetrahydrofuryl)-5-fluorouracil [ftorafur] (studies on the syntheses of heterocyclic compounds. Part 703)

Synthesis of 1-(2-tetrahydrol'uryl)-5-fluorouracil [Ftorafur] ( 1 ) which is well known as an antitumor agent from 5-fluorouracil ( 2 ) with 2-alkoxytetrahydrofurans (4) is described. Among these reactions, the best yield was obtained by using 2-t-butoxytetrahydrofuran (4h).     

Syntheses of analgesics. Part XXX.. Conformational studies of diastereoisomeric quaternary ammonium salts of 1,2,3,4,5,6-Hexahydro-2,6-methano-3-benzazocines

The configuration of the quaternary ammonium salts (Va and Vb) from 3-benzyl-1,2,3,4,5,6-hexahydro-8-hydroxy-6,11-dimethyl-2,6-methano-3-benzazocine. (II) and 3-methyl-2-butenyl bromide was determined spectroscopically. Moreover, configurational studies on 3-benzyl (VIa and VIb) and 3-(3-methyl-2-butenyl)benzazocinium bromides (VIIa and VIIb) were also achieved.     

Studies on the syntheses of heterocyclic compounds. Part CCCXXIX. Syntheses of i-spiroisoquinoline derivatives by phenolic cyclization

Phenolic cyclization of 2-(3-hydroxyphenyl)-2-methylethylamine (XIIIa) and 2-(3-hydroxyphenyl)phenethylamine (XIIIb) with various carbonyl compounds afforded eight types of corresponding 1-spirocycloalkano- and 1-spiroheterocycloalkano-1,2,3,4-tetrahydroisoquinoline derivatives (1-VIII) and 1,1-disubstituted-1, 2,3,4-tetrahydroisoquinoline derivative (IX). The acetyl derivatives of VI and IX and the benzoyl derivatives of III and V were also prepared. In addition, a synthetic method for obtaining the starting phenethylamines was examined.