14444-77-0Relevant articles and documents
AN IMPROVED PROCESS FOR THE PREPARATION OF 4-(N, N-DISUBSTITUTEDAMINO) BUTYRALDEHYDE ACETALS
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Page 19, (2010/02/04)
The invention disclosed in this application relates to an improved process for the preparation of compounds of formula (I): R1R2NCH2CH2CH2CH(OR3)2; wherein, R1 = R2 = C1-C16 alkyl; C3-C7 cycloalkyl; R1 = C1-C16 alkyl; R2 = C3-C7 cycloalkyl; NR1R2 = pyrrolidino, piperidino, morpholino, thiomorpholino, R1 = C1-C6 alkyl; R2 = ArCH2; Ar =4-R4-C6H4-, R4 = MeO, EtO, Me, Et, NMe2, NEt2, SMe, SEt, etc; R3=C1-C6 alkyl; C3-C7 cycloalkyl which comprises: (i) Reacting 3-(N, N-disubstitutedamino)propyl halide of formula (XXI): R1R2NCH2CH2CH2X; wherein, R1, R2 = as defined above, X = C1 or Br, with magnesium in the presence of a solvent to get the Grrgnard reagent 3-(N, N-disubstitutedamino)-propylmagnesium halide; (ii) Reacting the resulting 3-(N, N-disubstitutedamino) propylmagnesium halide (Grignard reagent) with the trisubstituted orthoformate of formula (XVII): HC(OR5)(OR3)2; wherein, R3 and R5 is same or different and represent C1 to C6 alkyl, C3 to C7 cycloalkyl OR R3 is as defined above and R5 represents phenyl radical; (iii) Filtering off the resultant reaction mixture and distilling the filtrate to isolate the compound of the formula (I). These substituted butyraldehyde derivatives of the formula (I) are very important building blocks for the synthesis of various tryptamine derivatives. In particular 4-(N, N-dimethylamino)butyraldehyde dimethyl or diethyl acetals are crucial intermediates for the synthesis of commercially available anti-migraine drugs, like sumatriptan, zolmitriptan, and rizatriptan.
