Piperazine → Ethyl 4-[(4-(2-pyridyloxy)phenyl)methyl]piperazinecarboxylate
Reaction equation
N1CCNCC1.[N:7]1([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[O:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31]Cl)=[CH:27][CH:26]=1>>[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[O:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:31][N:10]2[CH2:11][CH2:12][N:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:8][CH2:9]2)=[CH:29][CH:30]=1Participants
Procedure
As depicted in Scheme 5, the known piperazine intermediate, for example, ethyl 1-piperazinecarboxylate (2000-2001 Aldrich Chemical catalog, pg 795), was reacted with the known methyl halide, for example 4-(2-pyridyloxy)phenylmethyl chloride (WO 97/26252) under basic conditions in an appropriate solvent, affording the corresponding ethyl ester, ethyl 4-[(4-(2-pyridyloxy)phenyl)methyl]piperazinecarboxylate (AA). Intermediate (AA) was then oxidized with, for example 30% hydrogen peroxide, providing the corresponding 4-oxide, ethyl 4-[(4-(2-pyridyloxy)phenyl)methyl]-4-oxypiperazinecarboxylate (BB), which in turn was decarboxylated with a strong aqueous base, providing the corresponding free piperazine 4-oxide, for example 2-[4-(4-oxypiperazin-1-ylmethyl)phenoxy]pyridine (CC).
Sources & evidence
- ORD record
- ord-c6a66dcedd904120a1001b173dfd66d5
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07365082B2
Reaction notes
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