Piperidine → 4-(Piperidine-1-sulfonyl)-benzoic acid

HRID 1676950Notes

Reaction equation

HRID 1676950 reaction equation
Cl[S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(N(CC)CC)C.[NH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>ClCCl>[N:21]1([S:2]([C:5]2[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][CH:6]=2)(=[O:4])=[O:3])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 8471TriethylamineHCID 823854-(Chlorosulfonyl)benzoic acid

Product 1

HCID 7465554-(Piperidine-1-sulfonyl)-benzoic acidYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4-(Chlorosulfonyl)benzoic acid (CAS 10130-89-9) (441 mg, 2.0 mmol) and triethylamine (202 mg, 2.0 mmol) are dissolved in dichloromethane (20 mL) and stirred under nitrogen while piperidine (340 mg, 4.0 mmol) in dichloromethane (5 mL) is added to the mixture at room temperature. After 18 h the reaction mixture is concentrated. The crude material is slurried in aqueous NaHCO3, washed with diethyl ether, and separated. Ethyl acetate is added to the aqueous layer and the pH adjusted to 2 with 1N HCl. The layers are separated and the aqueous layer is extracted with EtOAc (2×). The EtOAc extracts are combined, washed with brine, dried over Na2SO4 and evaporated. The residue is purified by silica-gel column chromatography (0-8% MeOH/CH2Cl2 gradient) to give 350 mg (65%) of the title compound. MS (ES+) 270.1 (M+H)+.

Workup

  1. additionis added to the mixture at room temperature
  2. concentrationAfter 18 h the reaction mixture is concentrated
  3. washwashed with diethyl ether
  4. customseparated
  5. additionEthyl acetate is added to the aqueous layer
  6. customThe layers are separated
  7. extractionthe aqueous layer is extracted with EtOAc (2×)
  8. washwashed with brine
  9. dry with materialdried over Na2SO4
  10. customevaporated
  11. customThe residue is purified by silica-gel column chromatography (0-8% MeOH/CH2Cl2 gradient)

Sources & evidence

ORD record
ord-97ad9400e9df492d92ccd6287e594d59
Source dataset
uspto-grants-2011_08
Patent number
US08008296B2

Reaction notes

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