Hydrochloric Acid → HCID 14305409, compound

HRID 623254Notes

Reaction equation

HRID 623254 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.CCOCC.O>[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

10

Reactant 6

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

Product 1

HCID 14305409HCID 14305409, compoundYield 36.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 344 mls (0.74 mol) of 2.15 molar lithium diisopropyl amide (in hexanes) in 1.8 liters dry tetrahydrofuran cooled to -70° under nitrogen was added dropwise a solution of 65 g (0.67 mol) of 2-fluoropyridine in 300 mls dry tetrahydrofuran such that the temperature was maintained below -65°. After the solution was stirred 4 hours at -70°, 73.5 g (1.15 mol) of sulfur dioxide was added dropwise while the temperature was maintained below -65°. The suspension was stirred 1 hour at -70° and allowed to warm to room temperature. The reaction was diluted with ether and the precipitate was collected and washed with ether under a nitrogen atmosphere. The solid was stirred and dissolved in 550 mls acetic acid. 89 g (0.67 mol) of N-chlorosuccinimide was added portionwise while the temperature was maintained below 20°. After stirring an additional 30 minutes at room temperature, the reaction was evaporated, diluted with water, and extracted with ether. The combined organic layers were washed with saturated sodium bicarbonate solution until gas evolution ceased, dried over magnesium sulfate, and evaporated to a dark liquid which was dissolved in 900 mls methylene chloride and cooled to 0° under nitrogen. 244 g (3.3 mol) of t-butyl amine was added dropwise while the temperature was maintained below 10°. The reaction was stirred at room temperature for 20 hours and poured into water, acidified with 1 normal hydrochloric acid, and extracted with methylene chloride. The combined organic layers were washed with brine, dried over magnesium sulfate and evaporated to a dark liquid which was purified by flash chromatography to afford 56.3 g (36%) white solid: m.p. 95°-97°; NMR (CDCl3, 200 MHz), 1.25 (9H, s), 4.9 (NH), 7.3-7.4 (1H, m), 8.3-8.5 (2H, m); IR (nujol) 3290, 1590, 1570, 1320, 1160 cm-1.

Workup

  1. temperaturewas maintained below -65°
  2. temperaturewas maintained below -65°
  3. stirringThe suspension was stirred 1 hour at -70°
  4. customthe precipitate was collected
  5. washwashed with ether under a nitrogen atmosphere
  6. stirringThe solid was stirred
  7. dissolutiondissolved in 550 mls acetic acid
  8. temperaturewas maintained below 20°
  9. stirringAfter stirring an additional 30 minutes at room temperature
  10. customthe reaction was evaporated
  11. additiondiluted with water
  12. extractionextracted with ether
  13. washThe combined organic layers were washed with saturated sodium bicarbonate solution until gas evolution
  14. dry with materialdried over magnesium sulfate
  15. customevaporated to a dark liquid which
  16. dissolutionwas dissolved in 900 mls methylene chloride
  17. temperaturecooled to 0° under nitrogen
  18. temperaturewas maintained below 10°
  19. stirringThe reaction was stirred at room temperature for 20 hours
  20. extractionextracted with methylene chloride
  21. washThe combined organic layers were washed with brine
  22. dry with materialdried over magnesium sulfate
  23. customevaporated to a dark liquid which
  24. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-6752bc2af8384d11b11fd0fa5b47ccd1
Source dataset
uspto-grants-1988_09
Patent number
US04774337

Reaction notes

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