4-Piperidinecarboxylic acid → HCID 58653686, compound

HRID 1676037Notes

Reaction equation

HRID 1676037 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[C:4](F)[C:3]=1[N+:9]([O-:11])=[O:10].[CH3:12][O:13][C:14](=[O:24])[CH2:15][CH:16]([NH2:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+].[NH:31]1[CH2:36][CH2:35][CH:34]([C:37]([OH:39])=[O:38])[CH2:33][CH2:32]1>CS(C)=O.O>[CH3:12][O:13][C:14](=[O:24])[CH2:15][CH:16]([NH:23][C:2]1[C:3]([N+:9]([O-:11])=[O:10])=[C:4]([N:31]2[CH2:36][CH2:35][CH:34]([C:37]([OH:39])=[O:38])[CH2:33][CH2:32]2)[CH:5]=[CH:6][CH:7]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 37734-Piperidinecarboxylic acidHCID 11430Potassium CarbonateHCID 879221,3-Difluoro-2-nitrobenzeneHCID 2755328Methyl 3-amino-3-phenylpropionate

Product 1

HCID 58653686HCID 58653686, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a solution of 2,6-difluoronitrobenzene (272 mg, 1.71 mmol) in DMSO (2 mL) was added methyl-3-amino-3-phenylpropanoate (553 mg, 2.57 mmol) and potassium carbonate (709 mg, 5.13 mmol), and the suspension stirred at room temperature for 24 hours. 4-Piperidinecarboxylic acid (335 mg, 2.59 mmol) was added, and the resulting suspension stirred at room temperature for 24 hours, and then heated at 100° C. for 3 hours. The suspension was cooled to room temperature, and diluted with water. The aqueous solution was extracted with ethyl acetate, and the separated aqueous layer acidified with dilute hydrochloric acid (pH<4), and re-extracted with ethyl acetate. The second organic extracts were evaporated in vacuo, and the residue purified by flash column chromatography on silica gel, eluting with a mixture of dichloromethane and methanol (96:4) to afford the title compound, 1H NMR: (CDCl3) 7.36-7.22 (m, 5H), 7.02 (t, J=8.06, 1H), 6.34 (dd, J=8.06, 1.10, 1H), 6.19 (d, J=8.06, 1H), 4.89-4.85 (m, 1H), 3.66 (s, 3H), 3.25-3.21 (m, 2H), 2.87-2.77 (m, 4H), 2.48-2.41 (m, 1H), 2.02-1.82 (m, 4H).

Workup

  1. stirringthe resulting suspension stirred at room temperature for 24 hours
  2. temperatureheated at 100° C. for 3 hours
  3. temperatureThe suspension was cooled to room temperature
  4. extractionThe aqueous solution was extracted with ethyl acetate
  5. extractionre-extracted with ethyl acetate
  6. customThe second organic extracts were evaporated in vacuo
  7. customthe residue purified by flash column chromatography on silica gel
  8. washeluting with a mixture of dichloromethane and methanol (96:4)

Sources & evidence

ORD record
ord-5b31cd8ca9a84066acbe8ccd964e92ef
Source dataset
uspto-grants-2011_08
Patent number
US08003806B2

Reaction notes

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