2-Fluoro-4-methylsulfonylphenol → 4-[3-(2-Fluoro-4-methanesulfonyl-phenoxymethyl)-[1,2,4]triazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 80645Notes

Reaction equation

HRID 80645 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[N:17][C:16]([CH2:19][O:20]S(C)(=O)=O)=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:25][C:26]1[CH:31]=[C:30]([S:32]([CH3:35])(=[O:34])=[O:33])[CH:29]=[CH:28][C:27]=1O>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:18]=[N:17][C:16]([CH2:19][O:20][C:27]3[CH:28]=[CH:29][C:30]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:31][C:26]=3[F:25])=[N:15]2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 161288422-Fluoro-4-methylsulfonylphenolHCID 577083784-(3-Methanesulfonyloxymethyl-[1,2,4]triazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester2×

Product 1

HCID 251758854-[3-(2-Fluoro-4-methanesulfonyl-phenoxymethyl)-[1,2,4]triazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(3-methanesulfonyloxymethyl-[1,2,4]triazol-1-yl) -piperidine-1-carboxylic acid tert-butyl ester (Intermediate 1, 0.222 g, 0.641 mmol), 2-Fluoro-4-methanesulfonyl-phenol (0.122 g, 0.641 mmol) and CsCO3 (0.250 g, 0.769 mmol) in acetonitrile (10 mL) was heated under reflux for 4 hours. After cooling, the solution was filtered through a pad of celite and the solvent was removed in vacuo. The residue was purified by flash chromatography on silica gel with Hexanes and EtOAc to afford the desired product. 1H NMR (CDCl3): δ 8.15 (1H, s), 7.62 (2H, m), 7.37 (1H, m), 5.25 (2H, s), 4.25 (3H, m), 3.05 (3H, s), 2.85 (2H, m), 2.18 (2H, m), 1.97 (2H, m), 1.43 (9H, s).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 4 hours
  3. temperatureAfter cooling
  4. filtrationthe solution was filtered through a pad of celite
  5. customthe solvent was removed in vacuo
  6. customThe residue was purified by flash chromatography on silica gel with Hexanes and EtOAc

Sources & evidence

ORD record
ord-f9c1cd8647364f3891fac19d3cc52c61
Source dataset
uspto-grants-2014_09
Patent number
US08846675B2

Reaction notes

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