Pyridine → tert-butyl (2S)-2-(5-[4-(hydroxymethyl)phenoxymethyl]-1,2,4-oxadiazol-3-yl)-1-piperidinecarboxylate

HRID 397649Notes

Reaction equation

HRID 397649 reaction equation
N[C@@:2]1(/[CH:15]=[N:16]\[O:17][C:18](=O)[CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([CH2:27][OH:28])=[CH:23][CH:22]=2)[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[N:30]1C=CC=CC=1>>[OH:28][CH2:27][C:24]1[CH:25]=[CH:26][C:21]([O:20][CH2:19][C:18]2[O:17][N:16]=[C:15]([C@@H:2]3[CH2:7][CH2:6][CH2:5][CH2:4][N:3]3[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[N:30]=2)=[CH:22][CH:23]=1

Participants

3

Reactant 2

HCID 1049PyridineHCID 140460767tert-butyl (2S)-2-amino-2-[(Z)-[2-[4-(hydroxymethyl)phenoxy]acetyl]oxyiminomethyl]piperidine-1-carboxylate

Product 1

HCID 57274150tert-butyl (2S)-2-(5-[4-(hydroxymethyl)phenoxymethyl]-1,2,4-oxadiazol-3-yl)-1-piperidinecarboxylate

Procedure

tert-Butyl (Z)-(2S)-2-amino[(2-[4-(hydroxymethyl)phenoxy]acetyloxy)imino]methyl-1-piperidinecarboxylate (see Preparation 12] (2.94 g) was dissolved in pyridine (30 ml) and heated under reflux for 18 hours. The reaction mixture was cooled and the solvent removed under reduced pressure. The residue was partitioned between ethyl acetate and water, the organic layer was separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 50:50 changing to 0:100 (in 10% increments), by volume, hexane:ethyl acetate to afford tert-butyl (2S)-2-(5-[4-(hydroxymethyl)phenoxymethyl]-1,2,4-oxadiazol-3-yl)-1-piperidinecarboxylate (1.06 g).

Workup

  1. customPreparation 12] (2.94 g)
  2. temperatureheated
  3. temperatureunder reflux for 18 hours
  4. temperatureThe reaction mixture was cooled
  5. customthe solvent removed under reduced pressure
  6. customThe residue was partitioned between ethyl acetate and water
  7. customthe organic layer was separated
  8. dry with materialdried over magnesium sulphate
  9. customthe solvent removed under reduced pressure
  10. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 50:50 changing to 0:100 (in 10% increments), by volume, hexane

Sources & evidence

ORD record
ord-263dc112a84d4161b37ca21b86569cfc
Source dataset
uspto-grants-2003_08
Patent number
US06610707B1

Reaction notes

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