Hydrochloric Acid → [4-(Pyridin-2-ylsulfamoyl)-phenyl]-acetic acid ethyl ester

HRID 858073Notes

Reaction equation

HRID 858073 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([O:10][C:11](=[O:23])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1)[CH3:9].Cl.O>N1C=CC=CC=1>[CH2:8]([O:10][C:11](=[O:23])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([S:19](=[O:20])(=[O:21])[NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:15][CH:14]=1)[CH3:9]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 104392-AminopyridineHCID 10467900(4-Chlorosulfonyl-phenyl)-acetic acid ethyl ester

Product 1

HCID 58762849[4-(Pyridin-2-ylsulfamoyl)-phenyl]-acetic acid ethyl esterYield 27%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

A stirred solution of 2-aminopyridine (282 mg, 3.0 mmol) in dry pyridine (5.0 mL) was treated with (4-chlorosulfonyl-phenyl)-acetic acid ethyl ester (prepared according to the procedure of Kawashima et. al, as described in Chem. Pharm. Bull. 1995, 43(7), 1132) dropwise at 0–5° C. under argon. Upon completion of addition, the reaction was slowly warmed to 25° C. The reaction was stirred at 25° C. until no starting materials remained. At this time, the reaction was cooled to 0° C. and was acidified to pH=5 with a 1.0M aqueous hydrochloric acid solution. The reaction mixture was poured into water and was extracted with ethyl acetate. The combined organic extracts were washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 3/97 methanol/methylene chloride) afforded [4-(pyridin-2-ylsulfamoyl)-phenyl]-acetic acid ethyl ester (0.26 g, 27%) as a colorless solid; 1H NMR (CDCl3, 300 MHz) δH 13.67 (broad s, 1H), 8.30 (dd, J=5.9, 1.1 Hz, 1H), 7.86 (d, J=8.4 Hz, 2H), 7.65 (tt, J=8.1, 1.7 Hz, 1H), 7.50–7.30 (m, 3H), 6.77 (t, J=6.3 Hz, 1H), 4.12 (q, J=7.0 Hz, 2H), 3.63 (s, 2H), 1.22 (t, J=7.0 Hz, 3H); LRMS for C15H16N2O4S (M+H)+ at m/z=321.

Workup

  1. customprepared
  2. customdropwise at 0–5° C.
  3. additionUpon completion of addition
  4. temperatureAt this time, the reaction was cooled to 0° C.
  5. extractionwas extracted with ethyl acetate
  6. washThe combined organic extracts were washed with water
  7. dry with materiala saturated aqueous sodium chloride solution, dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f421300cfcc840858f72134614e22a84
Source dataset
uspto-grants-2006_12
Patent number
US07148229B2

Reaction notes

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