2-(Bromomethyl)benzonitrile → tert-butyl (3RS,4RS)-3-(2-cyano-benzyloxy)-4-(4-fluoro-phenyl)-piperidine-1-carboxylate
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]2[OH:21])=[CH:4][CH:3]=1.Br[CH2:23][C:24]1[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=1[C:26]#[N:27]>>[C:26]([C:25]1[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=1[CH2:23][O:21][CH:9]1[CH:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:10]1)#[N:27]Participants
3
Procedure
In an analogous manner to that described in Example 9(a)-(c), by alkylating tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-hydroxy-piperidine-1-carboxylate [Example 3(b)] with 2-bromomethylbenzonitrile there was obtained tert-butyl (3RS,4RS)-3-(2-cyano-benzyloxy)-4-(4-fluoro-phenyl)-piperidine-1-carboxylate, reduction of which using borane-dimethyl sulphide complex gave tert-butyl (3RS,4RS)-3-(2-aminomethyl-benzyloxy)-4-(4-fluoro-phenyl)-piperidine-1-carboxylate. Subsequent acylation with pyridine-2-carboxylic acid in the presence of EDC yielded tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-(2-{[(pyridine-2-carbonyl)-amino]-methyl}-benzyloxy)-piperidine-1-carboxylate as a white solid.
Sources & evidence
- ORD record
- ord-d07ff4a293944185800df981848368a0
- Source dataset
- uspto-grants-2000_11
- Patent number
- US06150526
Reaction notes
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