N-bromobutanimide → 5-(4-Bromomethylphenyl)-2-methyl-2H-tetrazole
Reaction equation
[CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)=[N:3]1.[Br:14]N1C(=O)CCC1=O>>[Br:14][CH2:13][C:10]1[CH:11]=[CH:12][C:7]([C:4]2[N:5]=[N:6][N:2]([CH3:1])[N:3]=2)=[CH:8][CH:9]=1Participants
Procedure
In a first step as depicted in Scheme 2, an appropriately substituted phenyl derivative, for example, the known compound 2-methyl-5-(4-methylphenyl)-1,2,3,4-tetrazole, is brominated with, for example N-bromosuccinimide and light, to afford the corresponding 5-[4-(bromomethyl)phenyl]-2-methyl-1,2,3,4-tetrazole (A1). Intermediate (A1) is then reacted under basic conditions with an appropriately substituted cyclic amine derivative, for example, the known compound 4-piperidone hydrochloride monohydrate, to afford the corresponding 1-{[4-(2-methyl-1,2,3,4-tetrazol-5-yl)phenyl]methyl}piperidin-4-one (B1). Intermediate (B1) is then reacted under acidic conditions with, for example sodium cyanide, to afford the corresponding nitrile compound, 4-hydroxy-1-{[4-(2-methyl(1,2,3,4-tetrazol-5-yl))phenyl]methyl}piperidine-4-carbonitrile (C1). Intermediate (C1) is esterified under acidic conditions with, for example ethanol, to afford the corresponding ethyl 4-hydroxy-1-{[4-(2-methyl-(1,2,3,4-tetrazol-5-yl))phenyl]methyl}piperidine-4-carboxylate (D1). The Grignard of an appropriately substituted halophenyl derivative, for example 4-trifluoromethoxybromobenzene, is reacted with intermediate (D1) to provide compounds of formula I-B, wherein X and Y are, for example hydroxyl. Example 2, set forth below, provides detailed methods to how compounds of formula I (-B) shown in Scheme 2 were prepared.
Sources & evidence
- ORD record
- ord-a18e5a3491734bedbacef103c990f4be
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08119563B2
Reaction notes
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