4-Chloro-3-nitrobenzoic acid → 1-(4-Chloro-3-nitrobenzoyl)piperidine

HRID 1581510Notes

Reaction equation

HRID 1581510 reaction equation
[C:1]([C:8]1[NH:9][CH:10]=[CH:11]N=1)([C:3]1NC=CN=1)=O.[Cl:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][C:15]=1[N+:23]([O-:25])=[O:24].N1CCCCC1>C(OCC)(=O)C>[Cl:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([N:9]2[CH2:8][CH2:1][CH2:3][CH2:11][CH2:10]2)=[O:20])=[CH:16][C:15]=1[N+:23]([O-:25])=[O:24]

Participants

5

Reactant 3

HCID 73204-Chloro-3-nitrobenzoic acidHCID 8082PiperidineHCID 5250894Bis-(1H-imidazol-2-YL)-methanone

Product 1

HCID 7590631-(4-Chloro-3-nitrobenzoyl)piperidineYield 97%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A 5-L flask was charged with ethyl acetate (2.3 L) and carbonyl diimidazole (500.0 g, 2.48 mol) to which 4-chloro-3-nitrobenzoic acid (402.5 g, 2.48 mol) was added in portions over 1 hour. The solution was stirred for an additional 1.5 hours. Piperidine (222.2 g, 2.60 mol) was added dropwise over 2 hours and the resulting solution was stirred for an additional 4 hours. The reaction mixture was washed sequentially, twice with 6N HCl solution (600 mL), twice with saturated NaHCO3 (250 mL), and finally with saturated NaCl (250 mL). The organic solution was dried over anhydrous Na2SO4 and filtered, and the solvent was removed in vacuo to yield 646 g (97%) of 4chloro-3-nitrobenzoyl-piperidine as a yellow crystalline solid with m.p.=76-78° C. IR: 1633, 1535, and 1440 cm−1. 1H NMR (500 MHz, CDCl3): δ7.92 (1H, d, J=1.5 Hz), 7.60 (1H, d, J=8.1 Hz), 7.56 (1H, dd, J=8.1 and 1.5 Hz), 3.70 (2H, br s), 3.35 (2H, br s), 1.70 (4H, br s), and 1.56 ppm (2H, br s).

Workup

  1. additionwas added in portions over 1 hour
  2. stirringthe resulting solution was stirred for an additional 4 hours
  3. washThe reaction mixture was washed sequentially, twice with 6N HCl solution (600 mL), twice with saturated NaHCO3 (250 mL)
  4. dry with materialThe organic solution was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-1df90bc07def47469c2855c261247528
Source dataset
uspto-grants-2004_05
Patent number
US06730677B2

Reaction notes

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