Lactams. XIII. Alkylation of Lactim Ethers : A Novel Synthetic Route to N-(2-Arylethyl) lactams from N-Unsubstituted Lactams

概要

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Treatment of the lactim ethers (10a-d, 11a-c), prepared from N-unsubstituted 5-, 6-, and 7-membered lactams (6a-d), with phenacyl bromide or 3,4-dimethoxyphenacyl bromide in N, N-dimethylformamide at 60°for 1-6 hr furnished the corresponding N-substituted lactams (21a-d, 22a-c) in good yields. Conversion of the lactam ketones (21a-d, 22a-c) into the N-(2-arylethyl) lactams (25a-d, 26a-c) through the lactam alcohols (23a-d, 24a-c) was effected in excellent overall yields by NaBH_4 reduction followed by catalytic hydrogenolysis. In contrast, the alkylations of O-methylvalerolactim (10b) or O-ethylvalerolactim (11b) with less reactive alkyl halides (relative to phenacyl bromide) such as MeI, EtI, PhCH_2Br, PhCH_2CH_2Br, and 3,4-(MeO)_2C_6H_3CH_2CH_2Br were found to give mixtures of the normally N-alkylated 2-piperidones and N-methyl-or N-ethyl-2-piperidone presumed to have formed by the O→N methyl or ethyl migration during the reactions. Alkylations of the δ-valerolactam anion with 2-arylethyl bromide or its equivalents could afford the corresponding N-substituted 2-piperidones, but in unacceptable yields.
社団法人日本薬学会の論文
1978-07-25