Triethylamine → N-(2-chloropyridin-3-yl)methanesulfonamide

HRID 898721Notes

Reaction equation

HRID 898721 reaction equation
[Cl:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:9][S:10](Cl)(=[O:12])=[O:11].C(N(CC)CC)C>ClCCl.O>[Cl:1][C:2]1[C:7]([NH:8][S:10]([CH3:9])(=[O:12])=[O:11])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 805282-Chloro-3-pyridylamine

Product 1

HCID 4201371N-(2-chloropyridin-3-yl)methanesulfonamideYield 93.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

2-Chloro-pyridin-3-ylamine (1.00 g, 7.75 mmol) in dichloromethane (20 mL) at 23° C. was treated with methane sulfonyl chloride (2.23 g, 19.4 mmol) and triethylamine (1.96 g, 19.4 mmol). After stirring for 48 hours, the reaction mixture was diluted with water, the layers were separated, and the aqueous phase was extracted with dichloromethane (2×). The organic layers were combined, dried over MgSO4, filtered, and the filtrate concentrated under reduced pressure. The residue was chromatographed on flash silica gel (20% ethyl acetate:hexanes), concentrated under reduced pressure, and added to a 10% aqueous sodium hydroxide solution (32 mL). The solution was stirred vigorously for about 0.5 hours until homogeneous. The solution was then neutralized to pH˜7 with 2N HCl, saturated with Na2SO4, and extracted with ethyl acetate (3×). The combined extracts were dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure to afford 1.5 g (93% yield) of the title compound. References: Tetrahedron Letters 38, 26, 4667-4670, 1997; Eur. J. Org. Chem. 2000, 1263-1270. 1H NMR (300 MHz, DMSO-d6) δ 3.12 (s, 3H), 7.46 (dd, J=4.5, 8.4 Hz, 1H), 7.89 (dd, J=1.5, 8.4 Hz, 1H), 8.27 (dd, J=1.5, 4.5 Hz, 1H), 9.72 (bs, 1H); MS (ESI) m/e 205 (M)−.

Workup

  1. customthe layers were separated
  2. extractionthe aqueous phase was extracted with dichloromethane (2×)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customThe residue was chromatographed on flash silica gel (20% ethyl acetate:hexanes)
  7. concentrationconcentrated under reduced pressure
  8. additionadded to a 10% aqueous sodium hydroxide solution (32 mL)
  9. stirringThe solution was stirred vigorously for about 0.5 hours until homogeneous
  10. extractionextracted with ethyl acetate (3×)
  11. dry with materialThe combined extracts were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-06e56cdf2e5e447981c7765d453de2ff
Source dataset
uspto-grants-2008_04
Patent number
US07351828B2

Reaction notes

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