Formaldehyde → 1,2,3,4-Tetrahydroisoquinoline
Reaction equation
C(NC([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][NH:9]1)=O)(C)(C)C.C=O>>[CH2:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:17][CH2:8][NH:9]1Participants
Procedure
U.S. Pat. No. 5,256,783 describes a method of producing decahydro(4aS, 8aS) isoquinoline-3(S)-carboxamides, by producing N-tertbutyldecahydro(4aS, 8as)isoquinoline-3(S)-carboxamide in which an amide is introduced into tertbutylamide. The method described in this patent comprises five steps (1) N-protecting L-phenylalanine with benzyl chloroformate, (2) forming a mixed acid anhydride into N-tertbutylamide (84.3%), (3) reacting the resulting amide with formaldehyde in the presence of an acid catalyst to form a tetrahydroisoquinoline compound (66%), (4) N-deprotecting this compound by catalytic reduction using Pd (79%), and (5) obtaining a decahydroisoquinoline compound using an Rh catalyst (59%). However, this method is problematic in that it requires many steps, it has a step with a low yield, Rh is expensive and the reaction has to be strictly controlled to maintain optical purity. Accordingly, the development of a simpler method is desirable.
Sources & evidence
- ORD record
- ord-6a5c0d3ba76e4b6c91287cdee3f7ddc2
- Source dataset
- uspto-grants-1999_11
- Patent number
- US05994545
Reaction notes
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