Water → (1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-indol-5-yl)(4-(4-chlorophenoxy)piperidin-1-yl)methanone

HRID 2170861Notes

Reaction equation

HRID 2170861 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[NH:20][CH:19]=[CH:18]4)=[O:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:29][CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].O>CN(C)C=O>[Si:32]([O:31][CH2:30][CH2:29][N:20]1[C:21]2[C:17](=[CH:16][C:15]([C:13]([N:10]3[CH2:11][CH2:12][CH:7]([O:6][C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:25][CH:24]=4)[CH2:8][CH2:9]3)=[O:14])=[CH:23][CH:22]=2)[CH:18]=[CH:19]1)([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 67168639HCID 67168639, compound

Product 1

HCID 67169173(1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-indol-5-yl)(4-(4-chlorophenoxy)piperidin-1-yl)methanoneYield 99%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (4-(4-chlorophenoxy)piperidin-1-yl)(1H-indol-5-yl)methanone (30 mg, 0.085 mmol, Step-1 of Example 353) and sodium hydride (60% in oil, 4 mg, 0.17 mmol) in N,N-dimethylformamide (1.5 mL) was added (2-bromoethoxy)(tert-butyl)dimethylsilane (24 mg, 0.10 mmol) at room temperature. After stirring at room temperature for 2 hours, the mixture was poured into water (20 mL) and extracted with ethyl acetate (20 mL). The organic layer was washed with water (20 mL), and dried over sodium sulfate. After removal of the solvent, the residue was purified by silica-gel column chromatography (NH-gel, eluting with ethyl acetate) to give 43 mg (>99% yield) of (1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-indol-5-yl)(4-(4-chlorophenoxy)piperidin-1-yl)methanone as orange oil. This material was treated with 2M aqueous hydrochloric acid solution (0.4 mL) and tetrahydrofuran (1.5 mL) at room temperature for 1 hour. The mixture was neutralized by saturated sodium hydrogen carbonate aqueous solution and extracted with ethyl acetate (3 mL). The organic layer was dried over sodium sulfate. After removal of the solvent, the residue was purified by silica-gel column chromatography (NH-gel, eluting with ethyl acetate) and then preparative LC-MS to give 7.1 mg (18% yield) of the title compound.

Workup

  1. extractionextracted with ethyl acetate (20 mL)
  2. washThe organic layer was washed with water (20 mL)
  3. dry with materialdried over sodium sulfate
  4. customAfter removal of the solvent
  5. customthe residue was purified by silica-gel column chromatography (NH-gel, eluting with ethyl acetate)

Sources & evidence

ORD record
ord-114e72fae912430dbb342511e876ff51
Source dataset
uspto-grants-2015_06
Patent number
US09051296B2

Reaction notes

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