Cesium carbonate → tert-butyl 4-(4-((4-(1H-tetrazol-1-yl)phenoxy)methyl)thiazol-2-yl)piperidine-1-carboxylate

HRID 2409110Notes

Reaction equation

HRID 2409110 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][CH:16]=[C:17]([CH2:19]Cl)[N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:21]1([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)[CH:25]=[N:24][N:23]=[N:22]1.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C>[N:21]1([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:19][C:17]3[N:18]=[C:14]([CH:11]4[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]4)[S:15][CH:16]=3)=[CH:28][CH:27]=2)[CH:25]=[N:24][N:23]=[N:22]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 5429104-(1H-1,2,3,4-tetrazol-1-yl)phenolHCID 57423790Tert-butyl 4-[4-(chloromethyl)-1,3-thiazol-2-yl]piperidine-1-carboxylate

Product 1

HCID 25024141tert-butyl 4-(4-((4-(1H-tetrazol-1-yl)phenoxy)methyl)thiazol-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(4-chloromethyl-thiazol-2-yl)-piperidine-1-carboxylic acid tert-butyl ester (549 mg), 4-tetrazol-1-yl-phenol (270 mg), Cs2CO3 (890 mg) in acetonitrile was heated under reflux overnight. After cooling, the reaction mixture was filtered through a pad of celite, concentrated in vacuo. Purification by chromatography (40-100% EtOAc/Hexanes) gave the desired product as a white solid. 1H NMR (CDCl3): δ 8.01 (1H, s), 7.61 (2H, d, J=8.8 Hz), 7.25 (1H, s), 7.15 (2H, d, J=8.8 Hz), 5.22 (2H, s), 4.2 (2H, br), 3.17 (1H, m), 2.87 (2H, m), 2.11 (2H, m), 1.73 (2H, m), 1.46 (9H, s).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux overnight
  3. temperatureAfter cooling
  4. filtrationthe reaction mixture was filtered through a pad of celite
  5. concentrationconcentrated in vacuo
  6. customPurification by chromatography (40-100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-587fb1fbb6944d25853d4de72e854155
Source dataset
uspto-grants-2014_08
Patent number
US08815886B2

Reaction notes

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