Sodium hydride → HCID 11522862, compound

HRID 1158266Notes

Reaction equation

HRID 1158266 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]([O:23][Si](C(C)(C)C)(C)C)[C:9]2[N:13]([CH3:14])[C:12]([S:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[N:11][CH:10]=2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].FC1C=C(C(O[Si](C(C)(C)C)(C)C)C2N(C)C(Cl)=NC=2)C=CC=1>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:8]([C:9]2[N:13]([CH3:14])[C:12]([S:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[N:11][CH:10]=2)[OH:23])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11604812HCID 11604812, compoundHCID 57597513HCID 57597513, compound

Product 1

HCID 11522862HCID 11522862, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4-{5-[(3-Fluoro-phenyl)-(tert-butyl-dimethyl-silanyloxy)-methyl]-1-methyl-1H-imidazol-2-ylsulfanyl}-1-methyl-piperidine. To a 0° C. solution of 1-methyl-piperidine-thiol (1.5 equivalents) in THF (0.2 M) is added NaH (60% dispersion in oil, 1.5 equivalents). After 30 min, 5-[(3-fluoro-phenyl)-(tert-butyl-dimethyl-silanyloxy)-methyl]-2-chloro-1-methyl-1H-imidazole (1 equivalent) in THF (1 M) is added dropwise. The mixture is heated at reflux until HPLC analysis shows consumption of the starting material. The reaction mixture is cooled to rt, quenched with satd. aq. NH4Cl, and extracted with EtOAc (2×). The combined organic extracts are washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude material is purified by HPLC or flash column chromatography to provide the desired product.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux until HPLC analysis
  3. customconsumption of the starting material
  4. customquenched with satd
  5. extractionaq. NH4Cl, and extracted with EtOAc (2×)
  6. washThe combined organic extracts are washed with water and brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material is purified by HPLC or flash column chromatography

Sources & evidence

ORD record
ord-3f60e70015524b2884f81892bdae5868
Source dataset
uspto-grants-2010_10
Patent number
US07807837B2

Reaction notes

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