Acetone → HCID 58852277, compound

HRID 1716609Notes

Reaction equation

HRID 1716609 reaction equation
[F:1][C:2]1[C:3]([CH3:28])=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH:17]4[CH2:25][C:24]5[C:19](=[CH:20][CH:21]=[C:22]([F:26])[CH:23]=5)[CH2:18]4)[CH2:12][CH2:11]3)[C:6]=2[CH:27]=1.[Li]C(C)(C)C.[CH3:34][C:35]([CH3:37])=[O:36]>C1COCC1>[F:1][C:2]1[C:3]([CH3:28])=[CH:4][C:5]2[N:9]=[C:8]([C:35]([OH:36])([CH3:37])[CH3:34])[N:7]([CH:10]3[CH2:11][CH2:12][N:13]([CH2:16][CH:17]4[CH2:25][C:24]5[C:19](=[CH:20][CH:21]=[C:22]([F:26])[CH:23]=5)[CH2:18]4)[CH2:14][CH2:15]3)[C:6]=2[CH:27]=1

Participants

5

Reactant 3

HCID 180AcetoneHCID 588522736-fluoro-1-[1-(5-fluoro-indan-2-ylmethyl)-piperidin-4-yl]-5-methyl-1H-benzoimidazoleHCID 178418306HCID 178418306, compound

Product 1

HCID 58852277HCID 58852277, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-fluoro-1-[1-(5-fluoro-indan-2-ylmethyl)-piperidin-4-yl]-5-methyl-1H-benzoimidazole (25 mg, 0.065 mmol) in anhydrous THF (2 mL) was added tert-BuLi (0.058 mL, 1.7 M in pentane) at −78° C. After stirring for 10 minutes, anhydrous acetone (0.008 mL) was added and the reaction mixture was stirred at −78° C. for 40 minutes. After quenching with 1 M HCl (0.2 mL) the mixture was allowed to warm to rt. The solvent was removed under reduced pressure and the residue was diluted with ethyl acetate. The organic layers were washed with saturated NaHCO3, brine, and dried over Na2SO4. The extracts were removed and the residue was purified by flash chromatography (20/1 CH2Cl2/CH3OH) to afford 2-{6-fluoro-1-[1-(5-fluoro-indan-2-ylmethyl)-piperidin-4-yl]-5-methyl-1H-benzoimidazol-2-yl}-propan-2-ol (5 mg, 17%) as a white solid.

Workup

  1. stirringthe reaction mixture was stirred at −78° C. for 40 minutes
  2. customAfter quenching with 1 M HCl (0.2 mL) the mixture
  3. customThe solvent was removed under reduced pressure
  4. additionthe residue was diluted with ethyl acetate
  5. washThe organic layers were washed with saturated NaHCO3, brine
  6. dry with materialdried over Na2SO4
  7. customThe extracts were removed
  8. customthe residue was purified by flash chromatography (20/1 CH2Cl2/CH3OH)

Sources & evidence

ORD record
ord-1409d9104ec64298bbb0c20f7db61eb4
Source dataset
uspto-grants-2010_09
Patent number
US07803816B2

Reaction notes

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