2-CHLOROPYRIDINE-4-SULFONYL CHLORIDE synthesis

Yield: 49%

Reaction Conditions:

Stage #1:4-Amino-2-chloropyridine with hydrogenchloride;sulfur dioxide;acetic acid;trifluoroacetic acid;sodium nitrite in water at 0; for 1 h;
Stage #2: with sulfur dioxide;copper(l) chloride;copper dichloride at 0; for 1.5 h;

Steps:

59 2-Chloropyridine-4-sulfonyl chloride
4-Amino-2-chloropyridine (1.29 g, 10 mmol), TFA (10 mL), and con HCl (5 mL) was treated with NaNO₂ (2.07 g, 30 mmol) in water (7.5 mL) at 0° C., then stirred for 1 h at 0° C.
The solution was filtered at -5° C. and added to a solution of CuCl (0.10 g, 0.7 mmol), CuCl₂ (0.67 g, 3.9 mmol) in HOAc containing dissolved SO₂ (60 mL) (prepared by bubbling SO₂ gas through HOAc at rt for 2 h) at 0° C.
The reaction mixture was stirred at 0° C. for 1.5 h and diluted with DCM (50 mL).
The reaction was washed with ice-water (2*50 mL), sat'd NaHCO₃ (2*50 mL), and brine (50 mL).
The organic layer was dried with Na₂SO₄, and concentrated to yield 2-chloropyridine-4-sulfonyl chloride (1.05 g, 49%); ¹H NMR: (400 MHz, DMSO-d₆) δ: 7.82-7.84 (m, 1H), 7.93 (s, 1H), 8.78-8.80 (m, 1H).

References:

FLATLEY DISCOVERY LAB;Cole, Bridget M.;Nugent, Richard A.;Smith, JR., Paul T. US2016/96835, 2016, A1 Location in patent:Paragraph 0108; 0109