Hydroxylamine → 3-p-Methoxyphenyl-1-methyl-4-piperidone oxime
Reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14](=O)[CH2:13][CH2:12][N:11]([CH3:16])[CH2:10]2)=[CH:5][CH:4]=1.C(O)(=O)C([O-])=O.N1CCCCC1=O.[NH2:30][OH:31]>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14](=[N:30][OH:31])[CH2:13][CH2:12][N:11]([CH3:16])[CH2:10]2)=[CH:5][CH:4]=1Participants
Procedure
Cis-8-methoxy-2-methyl-6-phenyl-1,2,3,4,4a,10b-hexahydrobenzo[c][1,6]naphthyridine is obtained by addition of 3-amino-2-p-methoxyphenylpropionic acid ethyl ester to acrylic acid ethyl ester, reductive methylation of 2-p-methoxyphenyl-3,3'-iminodipropionic acid diethyl ester (M.P. of the hydrogen oxalate 152°) with formaldehyde to obtain 2-p-methoxymethyl-N-methyl-3,3'-iminodipropionic acid diethyl ester, reaction of the latter compound to obtain 3-carbethoxy-5-(p-methoxyphenyl)-1-methyl-4-piperidone (M.P. of the hydrochloride 180°-182°), which is converted by hydrolysis and subsequent decarboxylation into 3-p-methoxyphenyl-1-methyl-4-piperidone (M.P. of the hydrogen oxalate 137°-138°). The resulting piperidone is reacted with hydroxylamine to obtain 3-p-methoxyphenyl-1-methyl-4-piperidone oxime (M.P. 121°-122°), the oxime is hydrogenated with Raney nickel to obtain 4-amino-3-p-methoxyphenyl-1-methyl-piperidine (mixture of the two diastereoisomers), the amino compound is treated with benzoyl chloride, cis-4-benzoylamino-3-p-methoxyphenyl-1-methylpiperidine (M.P. 164°-165°) is isolated from the reaction mixture, and the latter amide is cyclized with phosphorus oxychloride to obtain the desired benzonaphthyridine.
Sources & evidence
- ORD record
- ord-74df98f0b0a3477a9eb170b3b700dbbc
- Source dataset
- uspto-grants-1978_05
- Patent number
- US04087530
Reaction notes
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