Water → 2-(Azetidin-1-ylsulfonyl)-5-chloropyridine

HRID 1964710Notes

Reaction equation

HRID 1964710 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([SH:8])=[N:6][CH:7]=1.Cl([O-])(=O)(=O)=[O:10].[Na+].[ClH:15].[NH:16]1[CH2:19][CH2:18][CH2:17]1.C(N(CC)CC)C.[OH2:27]>C(Cl)Cl.Cl>[N:16]1([S:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:15])=[CH:7][N:6]=2)(=[O:10])=[O:27])[CH2:19][CH2:18][CH2:17]1

Participants

8

Reactant 5

HCID 962WaterHCID 8471TriethylamineHCID 522606Sodium PerchlorateHCID 12308726Azetidine hydrochlorideHCID 1785277195-Chloropyridine-2-thiol

Product 1

HCID 666833922-(Azetidin-1-ylsulfonyl)-5-chloropyridineYield 46%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-5 °C

Procedure

5-Chloropyridine-2-thiol (1.00 g, 6.87 mmol) synthesized in Example (119a) was dissolved in methylene chloride (30 mL)/1N hydrochloric acid (30 mL), and cooled to −5° C. To the reaction solution, ice-cooled 7% aqueous sodium perchlorate solution (30 mL) was added dropwise while being kept at 0° C. or below, and stirring was carried out as it is for 15 minutes. The organic layer was extracted with a reparatory funnel ice-cooled in advance, and cooled to −78° C., a methylene chloride solution (10 mL) of commercially available azetidine hydrochloride (2.24 mg, 17.7 mmol) and triethylamine (1.8 mL, 12.9 mmol) was added, and the temperature was raised to 0° C., followed by stirring for 30 minutes. To the reaction solution, water (50 mL) was added, and extraction was carried out twice with ethyl acetate (30 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-60%) to afford the desired compound (735 mg, yield 46%) as a white solid.

Workup

  1. additionwas added dropwise
  2. customwhile being kept at 0° C. or below
  3. extractionThe organic layer was extracted with a reparatory funnel ice-
  4. temperaturecooled in advance
  5. temperaturecooled to −78° C.
  6. temperaturethe temperature was raised to 0° C.
  7. stirringby stirring for 30 minutes
  8. extractionextraction
  9. washThe organic layer was washed with saturated brine
  10. dry with materialsubsequently dried over anhydrous magnesium sulfate
  11. distillationThe solvent was distilled off under reduced pressure
  12. customthe resulting residue was purified
  13. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-60%)

Sources & evidence

ORD record
ord-a112dfc2f0804f3884812e4047f640aa
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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