FR-110302

1-萘醇,2,2-丁基-1,2,3,4-四氢-5-(2-喹啉甲氧基)-Chemical Name: (+)-2,2-Dibutyl-5-(2-quinolylmethoxy)-1,2,3,4-tetrahydro-1-naphthol
CAS No. 119257-22-6, 119257-23-7 (HCl), 119256-94-9 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Fujisawa (Originator)
合成路线:Alkylation of 5-methoxytetralone (I) with n-butyl iodide in the presence of lithium diisopropylamide (LDA) in dimethoxyethane afforded a mixture of mono- (II) and dialkylated (III) compounds that were separated by column chromatography.Hydrolysis of methoxy group of (III) by treatment with AlBr3 in refluxing benzene yielded phenol (IV),which was converted to ether (VI) by treatment with 2-(chloromethyl)quinoline (V) and K2CO3.The reduction of ketone (VI) with NaBH4 in MeOH provided racemic alcohol (VII).Resolution of racemate (VII) was performed by esterification with (S)-O-methylmandeloyl chloride (VIII),followed by chromatographic separation of the diastereomeric mixture.Then,basic hydrolysis of pure diastereomer (IX) provided the (+)-enantiomer.Alternatively,asymmetric reduction of tetralone (VI) with LiAlH4 in cold THF in the presence of the chiral auxiliary (S)-4-anilino-3-methylamino-1-butanol (X) or (S)-2-amino-3-methyl-1,1-diphenyl-1-butanol (XI) afforded (+)-alcohol (respectively).