Hydrochloric Acid → HCID 14305409, compound

HRID 275273Notes

Reaction equation

HRID 275273 reaction equation
C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[S:16](=[O:18])=[O:17].ClN1C(=O)CCC1=O.[C:27]([NH2:31])([CH3:30])([CH3:29])[CH3:28].Cl>O1CCCC1>[CH3:28][C:27]([NH:31][S:16]([C:15]1[C:10]([F:9])=[N:11][CH:12]=[CH:13][CH:14]=1)(=[O:18])=[O:17])([CH3:30])[CH3:29]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 1119Sulfur DioxideHCID 6385Tert-ButylamineHCID 97462-FluoropyridineHCID 31398ChlorosuccinimideHCID 2724682Lithium diisopropylamide

Product 1

HCID 14305409HCID 14305409, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 396 mL (0.740 mol) of 1.9 molar lithium diisopropylamide (in hexanes) in 1.5 L dry tetrahydrofuran cooled to -70° under nitrogen was added dropwise a solution of 65 g (0.670 mol) of 2-fluoropyridine in 150 mL dry tetrahydrofuran such that the temperature was maintained below -65°. The suspension was stirred at -70° for another 3.5 hours and 86 g (1.34 mol) of sulfur dioxide was added while maintaining the temperature below -65°. After stirring another 15 minutes at -70°, the reaction was allowed to warm to 0° and evaporated to half the original volume and diluted with ether. The white precipitate was collected under nitrogen, washed with ether, and dried. The solid was dissolved in 800 mL acetic acid and cooled to 10°-20°. To this stirred solution was added portionwise 99.4 g (0.740 mol) of N-chlorosuccinimide while maintaining the temperature below 20°. After stirring another 30 minutes, the suspension was evaporated, diluted with water and extracted with methylene chloride. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution until no more gas evolution, washed with brine, dried over magnesium sulfate, and filtered. The filtrate was cooled to -70° under nitrogen and to this stirred solution was added dropwise 199 g (2.7 mol) of t-butylamine. The suspension was poured into ice water, acidified with concentrated hydrochloric acid, and extracted with methylene chloride. The combined organic layers were washed with brine, dried over magnesium sulfate, and evaporated to an oil which was purified by flash chromatography to afford 29.1 g (19%) of a brown solid which was further washed with cold n-butylchloride to afford 22.4 g (14.5%) of a white solid: m.p. 95°-97°; NMR (CDCl3, 200 MHz) 1.25 (9H, s), 4.9 (NH), 7.35 (1H, m), 8.3-8.5 (2H, m).

Workup

  1. temperaturewas maintained below -65°
  2. temperaturewhile maintaining the temperature below -65°
  3. stirringAfter stirring another 15 minutes at -70°
  4. temperatureto warm to 0°
  5. customevaporated to half the original volume
  6. additiondiluted with ether
  7. customThe white precipitate was collected under nitrogen
  8. washwashed with ether
  9. customdried
  10. dissolutionThe solid was dissolved in 800 mL acetic acid
  11. temperaturecooled to 10°-20°
  12. temperaturewhile maintaining the temperature below 20°
  13. stirringAfter stirring another 30 minutes
  14. customthe suspension was evaporated
  15. additiondiluted with water
  16. extractionextracted with methylene chloride
  17. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution until no more gas evolution
  18. washwashed with brine
  19. dry with materialdried over magnesium sulfate
  20. filtrationfiltered
  21. temperatureThe filtrate was cooled to -70° under nitrogen and to this stirred solution
  22. extractionextracted with methylene chloride
  23. washThe combined organic layers were washed with brine
  24. dry with materialdried over magnesium sulfate
  25. customevaporated to an oil which
  26. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-3772eb810e074b4ab7daada88fd25c31
Source dataset
uspto-grants-1995_02
Patent number
US05393733

Reaction notes

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