4-Chloro-2-fluoro-1-nitrobenzene → 1-Carbethoxy-4-(5-chloro-2-nitroanilino)-piperidine

HRID 967365Notes

Reaction equation

HRID 967365 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4](F)[CH:3]=1.[NH2:12][CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:15][CH2:14]1>CN(C=O)C.C(Cl)Cl>[CH2:22]([O:21][C:19]([N:16]1[CH2:15][CH2:14][CH:13]([NH:12][C:4]2[CH:3]=[C:2]([Cl:1])[CH:7]=[CH:6][C:5]=2[N+:8]([O-:10])=[O:9])[CH2:18][CH2:17]1)=[O:20])[CH3:23]

Participants

5

Reactant 2

HCID 696914-Chloro-2-fluoro-1-nitrobenzeneHCID 100867Ethyl 4-amino-1-piperidinecarboxylate

Product 1

HCID 137921661-Carbethoxy-4-(5-chloro-2-nitroanilino)-piperidineYield 81%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2.03 g (11.6 mmol) of 4-chloro-2-fluoro-nitrobenzene in DMF (12.0 mL) at rt was added 2.00 g (11.6 mmol) of ethyl 4-amino-1-piperidinecarboxylate. A yellow precipitate formed within 30 min and the reaction was further diluted with DMF (12.0 mL) and CH2Cl2 (5.0 mL) and was shaken at 300 RPM overnight. The solvent was removed under reduced pressure and the resulting solid was dried under vacuum. The crude product was purified by flash chromatography (silica, 0-5% MeOH/CH2Cl2) to afford 2.83 g (81%) of the title compound. TLC (silica, 5% MeOH/CH2Cl2): Rf=0.4. MS (electrospray): m/z calculated for C14H18ClN3O4 [M++Na] 350.09, observed 350.0. 1H NMR (400 MHz, CDCl3): 8.13 (apparent d, J=9.1 Hz, 2H), 6.84 (d, J=2.0 Hz, 1H), 6.62 (dd, J=9.4, 2.3 Hz, 1H), 4.15 (q, J=14.9, 7.3 Hz, 2H), 4.08 (br d, J=12.4 Hz, 2H), 3.70-3.58 (m, 1H), 3.17-3.05 (m, 2H), 2.07 (br dd, J=13.1, 3.1 Hz, 2H), 1.63-1.50 (m, 2H), 1.28 (t, J=7.0 Hz, 3H).

Workup

  1. customA yellow precipitate formed within 30 min
  2. customThe solvent was removed under reduced pressure
  3. customthe resulting solid was dried under vacuum
  4. customThe crude product was purified by flash chromatography (silica, 0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-2c81330a86e74f07884cb27394b08b17
Source dataset
uspto-grants-2005_10
Patent number
US06953793B2

Reaction notes

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