Water → 1-Benzyl-4-((6-((tert-butyldimethylsilyl)oxy)hexyl)oxy)piperidine

HRID 1944857Notes

Reaction equation

HRID 1944857 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].O>CN(C=O)C>[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][O:24][Si:25]([C:28]([CH3:29])([CH3:31])[CH3:30])([CH3:26])[CH3:27])[CH2:12][CH2:11]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 784611-Benzylpiperidin-4-olHCID 4260352(6-Bromohexyloxy)-tert-butyldimethylsilane

Product 1

HCID 575169301-Benzyl-4-((6-((tert-butyldimethylsilyl)oxy)hexyl)oxy)piperidineYield 8.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Solid NaH (60% w/w in mineral oil, 352 mg, 4.6 mmol) was added to a stirring solution of 1-Benzyl-4-hydroxypiperidine (841 mg, 4.4 mmol) in DMF (50 mL) at 0° C. The resulting suspension was stirred for 5 min then Intermediate 19 (2.6 g, 8.8 mmol) was added. The reaction mixture was warmed to rt then heated to 70° C. over night. The resulting solution was cooled then pour into H2O (100 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with H2O (100 mL), brine (100 mL), dried over Na2SO4, and concentrated to give crude either 2.96 g as yellow oil. Chromatography (1:3, hexanes/EtOAc) afforded the title compound (157 mg, 8%) as clear oil. ES/MS calcd for C24H44NO2Si+ 406.3. Found m/z=406.3 (M+H)+.

Workup

  1. temperaturethen heated to 70° C. over night
  2. temperatureThe resulting solution was cooled
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organic layers were washed with H2O (100 mL), brine (100 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give crude either 2.96 g as yellow oil

Sources & evidence

ORD record
ord-f3ecbffbadf9440e891b6c3d69674328
Source dataset
uspto-grants-2013_03
Patent number
US08394829B2

Reaction notes

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