Benzylethanolamine → (4-Benzylmorpholin-2-yl)methanol
Reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH:3]([CH2:7][OH:8])[CH2:2]1.C(C1OC1)Cl.[CH2:14](NCCO)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[CH2:14]([N:1]1[CH2:6][CH2:5][O:4][CH:3]([CH2:7][OH:8])[CH2:2]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1Participants
Procedure
The first steps (B1 and B2) in the synthesis of the morpholin-2-yl methanol intermediates (compounds 54 and 56) of general reaction Scheme B, is to react epichlorohydrin with N-benzylethanolamine to form (4-benzylmorpholin-2-yl)methanol. (R) or (S) stereoisomers as appropriate, are formed using either the (R) or (S) form of epichlorohydrin. The reaction may take place in solution or in an organic solvent, such as a mixture of water and isopropanol. A preferred solvent is 1:1 water/isopropanol. Beneficially, epichlorohydrin may be dissolved in a pre-formed solution of N-benzylethanolamine. Conveniently, the reaction may be performed at room temperature (e.g. between 20 and 25° C.; preferably between 23 and 25° C.), and optionally may be continued at a lower temperature, such as −20° C. At −20° C. the reaction may be continued overnight (e.g. for a further 8 to 16 hours).
Sources & evidence
- ORD record
- ord-3739082a8bb54365bc9ee89a7d45b15f
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09079895B2
Reaction notes
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