Sodium Cyanide → HCID 57831205, compound
Reaction equation
[CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][N:14]3[CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]3)=[CH:9][CH:8]=2)=[N:3]1.[C-:21]#[N:22].[Na+]>>[OH:20][C:17]1([C:21]#[N:22])[CH2:18][CH2:19][N:14]([CH2:13][C:10]2[CH:9]=[CH:8][C:7]([C:4]3[N:5]=[N:6][N:2]([CH3:1])[N:3]=3)=[CH:12][CH:11]=2)[CH2:15][CH2:16]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-bd17e346030b4b63872aa2c10a0524d1
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08119563B2
Reaction notes
Loading…