Sodium hydride → HCID 11522862, compound

HRID 1786450Notes

Reaction equation

HRID 1786450 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. Step C. (3-Fluoro-phenyl)-[3-methyl-2-(1-methyl-piperidin-4-ylsulfanyl)-3H-imidazol-4-yl]-methanol. A solution of 4-{5-[(3-fluoro-phenyl)-(tert-butyl-dimethyl-silanyloxy)-methyl]-1-methyl-1H-imidazol-2-ylsulfanyl}-1-methyl-piperidine (1 equiv.) in THF (0.2 M) is treated with tetrabutylammonium fluoride (1.2 equiv.). When the reaction is complete, the solution is diluted with satd. aq. NaHCO3 and extracted with EtOAc. The organic layer is dried over anhydrous Na2SO4. The crude material is purified by chromatography or recrystallization. This material can then be oxidized to form the corresponding sulfoxide (A3 is S(O)), or sulfone (A3 is S(O2)) as described in Example XVI, Scheme XI.

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-162b6e4d486440c3b824c1d7e9705d69
Source dataset
uspto-grants-2009_03
Patent number
US07507756B2

Reaction notes

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