Sodium hydride → HCID 10365867, compound

HRID 227277Notes

Reaction equation

HRID 227277 reaction equation
C([O:3][C:4](=[O:30])[C:5]1[CH:10]=[C:9]([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=4)[NH:20][CH:19]=3)[CH2:14][CH2:13]2)[CH:8]=[CH:7][C:6]=1[O:28][CH3:29])C.[H-].[Na+]>CN(C=O)C>[CH2:4]([N:20]1[C:21]2[C:26](=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=2)[C:18]([CH:15]2[CH2:16][CH2:17][N:12]([CH2:11][C:9]3[CH:8]=[CH:7][C:6]([O:28][CH3:29])=[C:5]([CH:10]=3)[C:4]([OH:3])=[O:30])[CH2:13][CH2:14]2)=[CH:19]1)[CH2:5][CH2:6][CH3:7]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 688940515-[4-(6-fluoro-1H-indol-3-yl)-piperidin-1-ylmethyl]2-methoxybenzoic acid ethyl ester

Product 1

HCID 10365867HCID 10365867, compoundYield 14.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Under inert atmosphere, a solution of 0.07 g (0.17 mmol) of 5-[4-(6-fluoro-1H-indol-3-yl)-piperidin-1-ylmethyl]2-methoxybenzoic acid ethyl ester in 0.5 ml of anhydrous DMF was added dropwise to a suspension containing 0.012 g (0.24 mol) of sodium hydride (60% in mineral oil) in 1 ml of anhydrous DMF. After stirring at room temperature for 1 hour, a solution of 0.044 g (0.24 mol) of 1-bromobuthane in 0.5 ml of DMF was added. The reaction mixture was stirred at room temperature for 15 hours. The solvent was removed under reduced pressure. This ester was dissolved in a mixture of 1 ml of ethanol and hydrolysed with 2N NaOH at room temperature for 20 hours. The crude mixture was neutralised with 2N HCl aqueous solution and the solvent was removed under reduced pressure. The crude residue was purified by HPLC-MS chromatography affording 0.0053 g of the expected acid.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 15 hours
  2. customThe solvent was removed under reduced pressure
  3. dissolutionThis ester was dissolved in a mixture of 1 ml of ethanol and hydrolysed with 2N NaOH at room temperature for 20 hours
  4. customthe solvent was removed under reduced pressure
  5. customThe crude residue was purified by HPLC-MS chromatography

Sources & evidence

ORD record
ord-25de2fbb52f941698144e51579d29c16
Source dataset
uspto-grants-2009_07
Patent number
US07560471B2

Reaction notes

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