Piperidine → 2-(2-Nitrophenyl)propoxycarbonyl piperidine

HRID 1063509Notes

Reaction equation

HRID 1063509 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:8]([O:10][CH2:11][CH:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21])[CH3:13])=[O:9]>C1COCC1.CCOCC.O>[N+:20]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH:12]([CH3:13])[CH2:11][O:10][C:8]([N:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:9])([O-:22])=[O:21]

Participants

6

Reactant 2

HCID 8082PiperidineHCID 114479052-(2-Nitrophenyl)propyl chloroformate

Product 1

HCID 117020292-(2-Nitrophenyl)propoxycarbonyl piperidineYield 63.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of piperidine (22.8 mL, 230 mmol) in anhydrous THF (50 mL) was added dropwise to a solution of 2-(2-nitrophenyl)propyl chloroformate (28.20 g) in anhydrous THF (100 mL). The reaction mixture was then brought to reflux for 3 h and stirred at room temperature overnight. The solvent was evaporated to afford light brown oil. The mixture was diluted with ether (100 mL) and water (100 mL) was added. The organic phase was separated and the aqueous phase was re-extracted with ether (3×50 mL). The organic extracts were combined and dried over MgSO4, filtered, and the solvent was removed in vacuo. The residue was purified on a silica gel column. Elution of the column with 20% ethyl acetate in hexanes gave 16.54 g (56.6 mmol, 63.6% yield, 56.6% total yield) of 2-(2-nitrophenyl)propoxycarbonyl piperidine. 1H-NMR (600 MHz, DMF-d7): δ 7.88 (d, J=8.1 Hz, 1 H, Ar—H), 7.74 (m, 2 H, Ar—H), 7.53 (t, J=7.1 Hz, 1 H, Ar—H), 4.23 (m, 2 H, CH2), 3.54 (m, 1 H, CH), 3.24 (m, 4 H, CH2), 1.50 (m, 2 H, CH2), 1.35 (m, 7 H, CH2 and CH3). 13C-NMR (150 MHz, DMF-d7): δ 155.09 (OCOR), 151.50 (C ipso to NO2), 137.90 (C ipso to CH(CH3)CH2OCOR), 133.49 (C para to NO2), 129.31 (C para to CH(CH3)CH2OCOR), 128.44 (C ortho to CH(CH3)CH2OCOR), 124.35 (C ortho to N02), 69.45 (CH2OCOR), 45.08 (Cα to ring N), 34.26 (CH), 26.08 (Cβ to ring N), 24.69 (Cγ to ring N), 17.91 (CH3). TLC: 20% ethyl acetate in hexanes, Rf=0.4. Mass analysis (MALDI-TOF): calculated for C15H21N2O4 293.34, found 293.24.

Workup

  1. temperatureto reflux for 3 h
  2. customThe solvent was evaporated
  3. customto afford light brown oil
  4. additionwas added
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was re-extracted with ether (3×50 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customthe solvent was removed in vacuo
  10. customThe residue was purified on a silica gel column
  11. washElution of the column with 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-dbd4369a5fbb46eba771f7c10cd5aeae
Source dataset
uspto-grants-2005_11
Patent number
US06965040B1

Reaction notes

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