Imidazole → HCID 58168619, compound

HRID 1255270Notes

Reaction equation

HRID 1255270 reaction equation
[Si](Cl)(C(C)(C)C)(C)C.N1C=CN=C1.[Si:14]([O:21][CH2:22][CH2:23][C:24]1[CH:25]=[C:26]([CH2:29][C:30]#N)[S:27][CH:28]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].C(=O)([O-])[O-:33].[K+].[K+]>CN(C=O)C.C1COCC1.O>[Si:14]([O:21][CH2:22][CH2:23][C:24]1[CH:25]=[C:26]([CH2:29][CH2:30][OH:33])[S:27][CH:28]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 58168477HCID 58168477, compound2×

Product 1

HCID 58168619HCID 58168619, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

tert-Butyldimethylsilyl chloride (2.21 g) was added portionwise to a mixture of imidazole (1.00 g) and 2-(4-(2-hydroxyethyl)thiophen-2-yl)acetic acid [Aromatic Intermediate 20, step c] (1.3 g) in DMF (15 mL) at 20° C. over a period of 20 minutes. The resulting solution was stirred at 20° C. for 1 hour. The reaction mixture was diluted with THF (15 mL), cooled in ice-water, and treated with a solution of potassium carbonate (1.35 g) in water (15 mL). This mixture was stirred at 0° C. for 20 minutes. The mixture was partitioned between ethyl acetate and aqueous brine, and the phases separated. The organic layer was washed twice with aqueous brine, dried, filtered and the solvent removed under reduced pressure. The residue was dissolved in THF (40 mL), cooled in an ice bath and treated with borane tetrahydrofuran complex (1M in THF, 21 mL), added dropwise. The resultant solution was stirred at 20° C. for 2 hours. The reaction mixture was quenched by dropwise addition of methanol (10 mL) and the solvents were removed under reduced pressure. The crude product was purified by flash silica chromatography using 17% ethyl acetate in isohexane as solvent. Fractions containing the product were evaporated to dryness to afford the titled compound. Yield 1.25 g.

Workup

  1. stirringThis mixture was stirred at 0° C. for 20 minutes
  2. customThe mixture was partitioned between ethyl acetate and aqueous brine
  3. customthe phases separated
  4. washThe organic layer was washed twice with aqueous brine
  5. customdried
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. dissolutionThe residue was dissolved in THF (40 mL)
  9. temperaturecooled in an ice bath
  10. additiontreated with borane tetrahydrofuran complex (1M in THF, 21 mL)
  11. additionadded dropwise
  12. stirringThe resultant solution was stirred at 20° C. for 2 hours
  13. customThe reaction mixture was quenched by dropwise addition of methanol (10 mL)
  14. customthe solvents were removed under reduced pressure
  15. customThe crude product was purified by flash silica chromatography
  16. additionFractions containing the product
  17. customwere evaporated to dryness

Sources & evidence

ORD record
ord-96dc439dae4045229517376d496f44f0
Source dataset
uspto-grants-2013_06
Patent number
US08455483B2

Reaction notes

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