N-bromobutanimide → Methyl 2-(bromomethyl)-3-nitrobenzoate

HRID 272105ノート

反応式

HRID 272105 の反応式
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-:12])=[O:11])[C:5]=1[CH3:13].[Br:15]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-:12])=[O:11])[C:5]=1[CH2:13][Br:15]

参加物

4

反応物 2

HCID 67184N-bromobutanimideHCID 601165Methyl 2-methyl-3-nitrobenzoate

生成物 1

HCID 1487795Methyl 2-(bromomethyl)-3-nitrobenzoate

試薬・触媒・溶媒 1

HCID 5943Carbon Tetrachloride溶媒

実験手順

2-Methyl-3-nitrobenzoic acid methyl ester (commercially available) is treated in a solvent such as carbon tetrachloride with N-bromosuccinimide under light to produce 2-bromomethyl-3-nitrobenzoic acid methyl ester. This benzylic bromide is treated in a solvent such as dimethylformamide with [2-(3-amino-2,6-dioxo-piperidin-1-yl)-ethyl]-phosphonic acid diethyl ester (for the preparation of this compound, see below) in the presence of a base such as triethylamine. The coupled product is then reduced by hydrogenation (Bioorg. Med. Chem. Lett., (1999), 9, 1625) to afford the desired analog. [2-(3-amino-2,6-dioxo-piperidin-1-yl)-ethyl]-phosphonic acid diethyl ester is obtained according to a procedure such as that reported in J. Med. Chem., (2003) 46, 3793. Accordingly, benzyloxycarbonyl-protected glutaric acid is treated in a solvent such as acetonitrile with triethylamine, 1-hydroxybenzotriazole, diethyl 2-aminoethylphosphonate and 1,3-dicyclohexylcarbodiimide. After the reaction is complete, the solvent is removed and the residue is purified by chromatography to generate the cyclic product, which is subjected to hydrogen in the presence of palladium catalysis to afford the desired intermediate.

出典と根拠

ORDレコード
ord-1e58ac76dd8c44cb974697e82c5bb90d
出典データセット
uspto-grants-2008_11
特許番号
US07452901B2

反応ノート

読み込み中…