Potassium Carbonate → HCID 67816134, compound

HRID 1054547Notes

Reaction equation

HRID 1054547 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:16]=[CH:15][C:6]2[NH:7][C:8]([CH2:10][CH2:11][CH2:12][CH2:13][OH:14])=[N:9][C:5]=2[CH:4]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:25][Si:26]([CH2:29][CH2:30][O:31][CH2:32]Cl)([CH3:28])[CH3:27]>CN(C)C=O>[F:18][C:2]([F:1])([F:17])[C:3]1[CH:16]=[CH:15][C:6]2[N:7]([CH2:32][O:31][CH2:30][CH2:29][Si:26]([CH3:28])([CH3:27])[CH3:25])[C:8]([CH2:10][CH2:11][CH2:12][CH2:13][OH:14])=[N:9][C:5]=2[CH:4]=1.[F:18][C:2]([F:1])([F:17])[C:3]1[CH:16]=[CH:15][C:6]2[N:7]=[C:8]([CH2:10][CH2:11][CH2:12][CH2:13][OH:14])[N:9]([CH2:32][O:31][CH2:30][CH2:29][Si:26]([CH3:28])([CH3:27])[CH3:25])[C:5]=2[CH:4]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether2×HCID 178520562HCID 178520562, compound

Product 2

HCID 67816134HCID 67816134, compoundYield 22.3%HCID 86705759HCID 86705759, compoundYield 15.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(5-Trifluoromethyl-1H-benzoimidazol-2-yl)-butan-1-ol (2.2 g, 0 mmol) was dissolved in N,N-dimethylformamide (25 ml). Potassium carbonate (1.47 g, 10.65 mmol) was added, and the reaction stirred at RT for 1 h. SEM-Cl (1.66 ml, 9.37 mmol) was added dropwise, and the reaction stirred at RT for 3 h. An additional amount of SEM-Cl (0.50 ml, 2.81 mmol) was added dropwise, and the reaction stirred for a further 1 h. The reaction mixture was filtered, then concentrated under reduced pressure. The residue was redissolved in EtOAc (30 ml), and washed with water (3×30 ml, some NaCl added to aid separation). The organic layer was then dried (MgSO4) and concentrated to afford a red oil. The crude material was purified by biotage FCC, eluting with 18-100% EtOAc in heptane to afford 511.1 mg (15.4%) of 4-[5-Trifluoromethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-butan-1-ol (regioisomer 1) and 738.6 mg (22.3%) of 4-[6-Trifluoromethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yl]-butan-1-ol (regioisomer 2) as yellow oils. Regioisomers was arbitrarily assigned.

Workup

  1. stirringthe reaction stirred at RT for 3 h
  2. stirringthe reaction stirred for a further 1 h
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was redissolved in EtOAc (30 ml)
  6. washwashed with water (3×30 ml
  7. additionsome NaCl added to aid separation)
  8. dry with materialThe organic layer was then dried (MgSO4)
  9. concentrationconcentrated
  10. customto afford a red oil
  11. customThe crude material was purified by biotage FCC
  12. washeluting with 18-100% EtOAc in heptane

Sources & evidence

ORD record
ord-d869726f23dd471b9d102948f1a737f6
Source dataset
uspto-grants-2016_07
Patent number
US09394310B2

Reaction notes

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