2,4-Dinitrophenol → 1-Tert-butoxycarbonyl-3-methylenepiperidine-4-acetic acid ethyl ester

HRID 1374143Notes

Reaction equation

HRID 1374143 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]=[C:10]([CH2:14]O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])OCC.[N+](C1C=C([N+]([O-])=O)C=CC=1O)([O-])=O.[C:35]([O:38][CH2:39][CH3:40])(=[O:37])[CH3:36]>C1(C)C(C)=CC=CC=1>[CH2:39]([O:38][C:35](=[O:37])[CH2:36][CH:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9][C:10]1=[CH2:14])[CH3:40]

Participants

6

Reactant 4

HCID 14932,4-DinitrophenolHCID 8857Ethyl AcetateHCID 22258851HCID 22258851, compoundHCID 53630039Ethylorthoformate

Product 1

HCID 110872871-Tert-butoxycarbonyl-3-methylenepiperidine-4-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
140 °C

Procedure

In 30 ml of xylene, 1.10 g of 1-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-3-methanol (which had been prepared by the method described in Tetrahedron, Vol. 54, No. 25, p. 7045, 1998), 914 mg of ethyl orthoformate and 130 mg of 2,4-dinitrophenol were dissolved, and the formed solution was heated to 140° C. and stirred for 7 hours while removing the ethanol as formed. The reaction liquid was cooled, then ethyl acetate was added thereto and the organic layer was successively washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and removed of the solvent by distillation. The resulting residue was purified on silica gel column chromatography (hexane/ethyl acetate=10/1) to provide 692 mg of 1-tert-butoxycarbonyl-3-methylenepiperidine-4-acetic acid ethyl ester. The product was dissolved in 20 ml of tetrahydrofuran, cooled to 0° C., 111 mg of lithium aluminium hydride was added thereto, and stirred for an hour. Then an excessive amount of sodium sulfate decahydrate was added to the reaction liquid and stirred for 15 minutes. The resulting mixture was filtered, and the filtrate was concentrated to provide 558 mg of crude 1-tert-butoxycarbonyl-3-methylenepiperidine-4-ethanol.

Workup

  1. customwhile removing the ethanol
  2. customas formed
  3. customThe reaction liquid
  4. temperaturewas cooled
  5. washthe organic layer was successively washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customremoved of the solvent by distillation
  8. customThe resulting residue was purified on silica gel column chromatography (hexane/ethyl acetate=10/1)

Sources & evidence

ORD record
ord-971d43f2ee474182871325fa1d2eacd6
Source dataset
uspto-grants-2007_01
Patent number
US07164024B2

Reaction notes

Loading…