Sulfuryl chloride → HCID 61795720, compound

HRID 2170172Notes

Reaction equation

HRID 2170172 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[S:9](Cl)(Cl)(=[O:11])=[O:10].C([NH:16][CH2:17][C:18]([O-:20])=[O:19])C.[CH3:21][CH2:22]N(C(C)C)C(C)C>C1COCC1>[Br:8][C:6]1[CH:7]=[C:2]([S:9]([NH:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])(=[O:11])=[O:10])[CH:3]=[N:4][CH:5]=1

Participants

6

Reactant 4

HCID 24648Sulfuryl chlorideHCID 693693,5-DibromopyridineHCID 81531DiisopropylethylamineHCID 19816828HCID 19816828, compound

Product 1

HCID 61795720HCID 61795720, compoundYield 36.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

3,5-Dibromopyridine (3.00 g, 12.7 mmol) was dissolved in THF (20 mL) and the solution cooled to −20° C. Isopropyl magnesium chloride-lithium chloride complex (2.76 g, 19.0 mmol) was added to the solution under the nitrogen atmosphere. The reaction mixture was stirred for 45 minutes and sulfuryl chloride (1.55 mL, 19.0 mmol) was added (at −20° C.). Stirring continued for additional 30 minutes and to this mixture was added THF (10 mL) solution containing ethylglycinate (7.07 g, 50.7 mmol) and DIPEA (11.1 mL, 63.3 mmol) at −20° C. The reaction mixture was allowed to reach room temperature and stirred for 20 minutes before quenching with the addition of aqueous solution of ammonium chloride. The aqueous solution was extracted with ethyl acetate (2×25 mL). The combined organic portion was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using CombiFlash (REDISEP®, silica gel, 40 g, 35% ethyl acetate/pet ether) to obtain ethyl 2-(5-bromopyridine-3-sulfonamido)acetate (1.50 g, 21.3%). LCMS Condition B-39: retention time 1.95 min, [M+1]=322.8. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10 (t, J=7.2 Hz, 3H), 3.89 (d, J=6.0 Hz, 2H), 3.98 (q, J=7.2 Hz, 2H), 8.39 (t, J=2.0 Hz, 1H), 8.62 (t, J=6.0 Hz, 1H), 8.92 (d, J=2.0 Hz, 1H), 8.98 (d, J=2.0 Hz, 1H).

Workup

  1. additionIsopropyl magnesium chloride-lithium chloride complex (2.76 g, 19.0 mmol) was added to the solution under the nitrogen atmosphere
  2. stirringStirring
  3. waitcontinued for additional 30 minutes and to this mixture
  4. customto reach room temperature
  5. stirringstirred for 20 minutes
  6. custombefore quenching with the addition of aqueous solution of ammonium chloride
  7. extractionThe aqueous solution was extracted with ethyl acetate (2×25 mL)
  8. dry with materialThe combined organic portion was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-b399fb0a87564f9b9e676c3a1952f936
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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