Sodium hydride → 3-((2-Bromophenyl)(3-methoxypropoxy)methyl)-1-(2-(trimethylsilyl)ethylsulfonyl)piperidine

HRID 2355315Notes

Reaction equation

HRID 2355315 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]([CH:12]1[CH2:17][CH2:16][CH2:15][N:14]([S:18]([CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])(=[O:20])=[O:19])[CH2:13]1)[OH:11].[H][H].CS(O[CH2:34][CH2:35][CH2:36][O:37][CH3:38])(=O)=O>C1COCC1>[Br:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]([O:11][CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH:12]1[CH2:17][CH2:16][CH2:15][N:14]([S:18]([CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])(=[O:19])=[O:20])[CH2:13]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 116939633-Methoxypropyl methanesulfonateHCID 59383049(2-Bromophenyl)(1-(2-(trimethylsilyl)ethanesulfonyl)piperidin-3-yl)methanolHCID 178418361HCID 178418361, compound

Product 1

HCID 593828433-((2-Bromophenyl)(3-methoxypropoxy)methyl)-1-(2-(trimethylsilyl)ethylsulfonyl)piperidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A 250-mL three neck flask fitted with a reflux condenser was charged with NaH (60% in mineral oil, 644 mg of material, 16.1 mmol, 5.0 equiv). Anhydrous THF (80 mL) was added. A solution of (2-bromophenyl)(1-(2-(trimethylsilyl)ethanesulfonyl)piperidin-3-yl)methanol (1.4 g, 3.22 mmol, 1.0 equiv) in 10 mL of THF was slowly added via syringe. After cessation of hydrogen evolution, a solution of 3-methoxypropyl methanesulfonate (2.2 g, 12.8 mmol, 4.0 equiv) in 10 mL of THF was added and the resulting mixture was heated to reflux. After 1.0 h the signals for the starting material in the LC-MS were consumed and a new peak with M+Na for the desired product was observed. The mixture was allowed to cool to rt and excess NaH was quenched with water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic fractions were washed with brine and purified by flash chromatography on silica gel (40 g) eluting with 0-25% EtOAc in hexanes. This afforded 3-((2-bromophenyl)(3-methoxypropoxy)methyl)-1-(2-(trimethylsilyl)ethylsulfonyl)piperidine (1.2 g, 73%) as a clear syrup containing a mixture of two diastereomers. No attempt was made to separate the diastereomers. MS ESI+ve m/z 506 (M+1).

Workup

  1. temperaturethe resulting mixture was heated to reflux
  2. customAfter 1.0 h the signals for the starting material in the LC-MS were consumed
  3. customexcess NaH was quenched with water
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic fractions were washed with brine
  7. custompurified by flash chromatography on silica gel (40 g)
  8. washeluting with 0-25% EtOAc in hexanes
  9. additionThis afforded 3-((2-bromophenyl)(3-methoxypropoxy)methyl)-1-(2-(trimethylsilyl)ethylsulfonyl)piperidine (1.2 g, 73%) as a clear syrup containing
  10. additiona mixture of two diastereomers
  11. customto separate the diastereomers

Sources & evidence

ORD record
ord-07d400bac2c04cc2a59c88b65a2a9053
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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