2-Nitrobenzenesulfonyl chloride → Diethyl 4-[2-(2-nitro-benzenesulfonylamino)-ethoxy]-pyridine-2,6-dicarboxylate

HRID 2173753Notes

Reaction equation

HRID 2173753 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:9]=[C:8]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:7]=1.[N+:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31](Cl)(=[O:33])=[O:32])([O-:24])=[O:23]>C(Cl)Cl.N1C=CC=CC=1>[N+:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31]([NH:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:9]=[C:8]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:7]=1)(=[O:33])=[O:32])([O-:24])=[O:23]

Participants

5

Reactant 2

HCID 155402-Nitrobenzenesulfonyl chloride2×HCID 66713944Diethyl 4-(2-Aminoethoxy)pyridine-2,6-dicarboxylate Hydrochloride

Product 1

HCID 66714285Diethyl 4-[2-(2-nitro-benzenesulfonylamino)-ethoxy]-pyridine-2,6-dicarboxylateYield 68.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 957 mg of diethyl 4-(2-amino-ethoxy)-pyridine-2,6-dicarboxylate monohydrochloride in 30 ml of DCM and 734 μl of pyridine, precooled to about 5° C., was added 798 mg of 2-nitrobenzenesulfonyl chloride. The mixture was warmed to room temperature and stirred for 2 hours. A further 244 μl of pyridine and 665 mg of 2-nitrobenzenesulfonyl chloride were then added thereto and stirring was continued for 15 hours. The mixture was washed with 25 ml of water and the aqueous phase was extracted 2× with 25 ml of DCM. The organic phases were combined, dried over MgSO4, concentrated under reduced pressure and purified by flash chromatography on silica (Merck EasyVarioPrep 150 g column, Si60 15-40 μm), using a gradient of 0 to 10% EtOAc in DCM. The fractions containing the desired product were combined and concentrated under reduced pressure. 960 mg of diethyl 4-[2-(2-nitro-benzenesulfonylamino)-ethoxy]-pyridine-2,6-dicarboxylate were obtained. 1H NMR (400 MHz, DMSO-d6): 1.35 (t, J=7.2 Hz, 6H); 3.41 (t, J=5.2 Hz, 2H); 4.22 (t, J=5.2 Hz, 2H); 4.39 (q, J=7.2 Hz, 4H); 7.50 (s, 2H); 7.80 (m, 2H); 7.92 (m, 1H); 8.04 (m, 2H); 8.40 (m, 1H). LC/MS (C): tr=3.50 min; [M+H]+: m/z 468.

Workup

  1. customprecooled to about 5° C.
  2. stirringstirring
  3. waitwas continued for 15 hours
  4. washThe mixture was washed with 25 ml of water
  5. extractionthe aqueous phase was extracted 2× with 25 ml of DCM
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. custompurified by flash chromatography on silica (Merck EasyVarioPrep 150 g column, Si60 15-40 μm)
  9. additionThe fractions containing the desired product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-86423fc1544b472eb5682cd0150f89dd
Source dataset
uspto-grants-2015_06
Patent number
US09056914B2

Reaction notes

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