Imidazole → 2-(5-(2-(tert-Butyldimethylsilyloxy)ethyl)thiophen-2-yl)ethanol

HRID 1689196Notes

Reaction equation

HRID 1689196 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C=CN=C1.[OH:14][CH2:15][CH2:16][C:17]1[S:21][C:20]([CH2:22][C:23](O)=[O:24])=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.C1COCC1>[Si:1]([O:24][CH2:23][CH2:22][C:20]1[S:21][C:17]([CH2:16][CH2:15][OH:14])=[CH:18][CH:19]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 28928tert-Butyldimethylsilyl chlorideHCID 579889872-(5-(2-Hydroxyethyl)thiophen-2-yl)acetic acid

Product 1

HCID 579893142-(5-(2-(tert-Butyldimethylsilyloxy)ethyl)thiophen-2-yl)ethanol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyldimethylsilyl chloride (6.63 g) was added portionwise to a solution of imidazole (2.99 g) and 2-(5-(2-hydroxyethyl)thiophen-2-yl)acetic acid (3.9 g) (example 4, step e) in DMF (50 mL) over 20 minutes. The resulting solution was stirred for 1 h. THF (50 mL) was then added and the reaction cooled in an ice bath. A solution of potassium carbonate (4.05 g) in water (50 mL) was then added and the mixture stirred for 20 min. The reaction was partitioned between ethyl acetate and brine. The organic layer was separated and washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated in vacuo. The residue was dissolved in THF (80 mL) and borane tetrahydrofuran complex (1M solution in THF, 62.8 mL) was added dropwise. The resulting solution was stirred for 2 h and quenched by dropwise addition of methanol (30 mL). The solvents were then evaporated in vacuo. Purification was by silica gel chromatography, eluting with 83:17 isohexane:ethyl acetate to give the subtitled compound as a yellow liquid. Yield 4.6 g.

Workup

  1. temperaturethe reaction cooled in an ice bath
  2. stirringthe mixture stirred for 20 min
  3. customThe reaction was partitioned between ethyl acetate and brine
  4. customThe organic layer was separated
  5. washwashed twice with brine
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customthe solvent evaporated in vacuo
  9. dissolutionThe residue was dissolved in THF (80 mL)
  10. additionborane tetrahydrofuran complex (1M solution in THF, 62.8 mL) was added dropwise
  11. stirringThe resulting solution was stirred for 2 h
  12. customquenched by dropwise addition of methanol (30 mL)
  13. customThe solvents were then evaporated in vacuo
  14. customPurification
  15. washeluting with 83:17 isohexane

Sources & evidence

ORD record
ord-fe4ef655f1224767a365fdf90afe1261
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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