Triethylamine → 4-((Tert-butyldimethylsilyl)oxy)piperidine

HRID 1842358Notes

Reaction equation

HRID 1842358 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.CCN(CC)CC.[Cl-].[C:16]([SiH:20]([CH3:22])[CH3:21])([CH3:19])([CH3:18])[CH3:17]>C(Cl)Cl.CN(C)C1C=CN=CC=1.O>[C:16]([Si:20]([CH3:22])([CH3:21])[O:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 79341Piperidin-4-olHCID 131722836Tert-butyldimethylsilane chloride3×

Product 1

HCID 114813284-((Tert-butyldimethylsilyl)oxy)piperidineYield 75.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

7.94 g (78.57 mmoles) of 4-hydroxypiperidine are placed in 175 mL of CH2Cl2 and 35 mL Et3N under nitrogen. At 0° C., a solution of 25 g (165 mmoles) of tert-butyldimethylsilane chloride in 350 mL of CH2Cl2 is added dropwise. The reaction medium is agitated overnight at ambient temperature then 2.36 g (15.7 mmoles) of tert-butyldimethylsilane chloride are added. After agitation for 4 h at ambient temperature, 0.69 g (0.55 mmoles) 4-dimethylaminopyridine and 2.36 g (15.7 mmoles) tert-butyldimethylsilane chloride are added. The reaction medium is agitated overnight at ambient temperature then diluted in water and extracted with CH2Cl2. After drying over MgSO4, the organic phases are evaporated and the residue obtained is purified by silica gel flash chromatography (CH2Cl2-MeOH—NH4OH, gradient 100:0:0 to 90:9:1 in 50 min). 12.71 g of intermediate 5a are thus obtained in the form of yellow oil (yield 75%). TLC silica gel 60 F 254 Merck, CH2Cl2-MeOH—NH4OH: 90:9:1, Rf=0.47.

Workup

  1. waitAfter agitation for 4 h at ambient temperature
  2. stirringThe reaction medium is agitated overnight at ambient temperature
  3. extractionextracted with CH2Cl2
  4. dry with materialAfter drying over MgSO4
  5. customthe organic phases are evaporated
  6. customthe residue obtained
  7. customis purified by silica gel flash chromatography (CH2Cl2-MeOH—NH4OH, gradient 100:0:0 to 90:9:1 in 50 min)

Sources & evidence

ORD record
ord-e44125438aae4c92aedda274871018af
Source dataset
uspto-grants-2015_02
Patent number
US08946225B2

Reaction notes

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