Hydrochloric Acid → (2S,3S,5S)-N-hydroxy-1-methyl-2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-3-carboxamide

HRID 61448Notes

Reaction equation

HRID 61448 reaction equation
[CH3:1][N:2]1[CH2:7][C@@H:6]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[CH2:5][C@H:4]([C:15]([O:17]C)=O)[C@H:3]1[C:19]([N:21]1[CH2:26][CH:25]=[C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1)=[O:20].[OH:33][NH2:34].Cl.C[O-].[Na+]>CO>[OH:33][NH:34][C:15]([C@H:4]1[CH2:5][C@H:6]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[CH2:7][N:2]([CH3:1])[C@@H:3]1[C:19]([N:21]1[CH2:26][CH:25]=[C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1)=[O:20])=[O:17]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 787HydroxylamineHCID 10942334Sodium MethoxideHCID 67304754Methyl (2s,3s,5s)-1-methyl-2-[(4-phenyl-3,6-dihydropyridin-1(2h)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-3-carboxylate

Product 1

HCID 86598248(2S,3S,5S)-N-hydroxy-1-methyl-2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-3-carboxamideYield 63.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of methyl (2S,3S,5S)-1-methyl-2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)carbonyl]-5-(pyridin-4-yloxy)piperidine-3-carboxylate (70 mg, 0.0002 mol) in methanol (0.6674 mL, 0.01648 mol) was added 1.640 M of N-hydroxyamine in Methanol (2.01 mL) made from the corresponding HCl salt and sodium methoxide. After stirred at rt for 1 h, the mixture was acidified with 1N HCl. The resultant mixture was applied directly on RP-HPLC to afford the product as a TFA salt (56 mg, 63.4%). MS (ESI): (M+H)+=437.1.

Sources & evidence

ORD record
ord-4b8696220c284b8eaf77bd7f68774891
Source dataset
uspto-grants-2016_09
Patent number
US09440958B2

Reaction notes

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