Hydrochloric Acid → HCID 14281500, compound

HRID 1193556Notes

Reaction equation

HRID 1193556 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][C:7]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2N)([C:10]#[CH:11])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].Cl.N([O-])=O.[Na+]>O>[C:1]([N:4]1[CH2:9][CH2:8][C:7]2([C:10](=[CH2:11])[C:14]3[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:13]=3[O:12]2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 14281497HCID 14281497, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 14281500HCID 14281500, compoundYield 25.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A stirred suspension of 19.4 g of 1-N-acetyl-4-(2-amino-4-fluorophenoxy)-4-ethynylpiperidine, 91 ml of water and 6.9 ml of hydrochloric acid was heated at reflux until the starting material dissolved. The mixture was then cooled to below 10°. To the mixture was added slowly, dropwise, 7.6 ml of concentrated hydrochloric acid at a rate such that the temperature did not exceed 10°. To the mixture was then added dropwise a solution of 5.09 g of sodium nitrite in 11 ml water, maintaining the temperature below 10°. The mixture was stirred at 5°-10° for 25-30 min and subsequently filtered into 145 ml of 30% hypophosphorous acid. The mixture was allowed to stand overnight in a cold room and at room temperature for 8 hr. The mixture was diluted with water, extracted twice with ether, washed with saturate sodium chloride solution and dried over anhydrous magnesium sulfate. The mixture was filtered and the filtrate was evaporated. The residue was filtered through 200 g of alumina and eluted with 600 ml of ether. Evaporation of solvent provided an oil, which crystallized on standing to yield 4.72 g (25.7%) of product, mp 114°-116°.

Workup

  1. temperaturewas heated
  2. temperatureat reflux until the starting material
  3. dissolutiondissolved
  4. temperatureThe mixture was then cooled to below 10°
  5. additionTo the mixture was added slowly
  6. customdid not exceed 10°
  7. temperaturemaintaining the temperature below 10°
  8. filtrationsubsequently filtered into 145 ml of 30% hypophosphorous acid
  9. waitto stand overnight in a cold room and at room temperature for 8 hr
  10. additionThe mixture was diluted with water
  11. extractionextracted twice with ether
  12. washwashed with saturate sodium chloride solution
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationThe mixture was filtered
  15. customthe filtrate was evaporated
  16. filtrationThe residue was filtered through 200 g of alumina
  17. washeluted with 600 ml of ether
  18. customEvaporation of solvent
  19. customprovided an oil, which
  20. customcrystallized

Sources & evidence

ORD record
ord-7ca981288a774c709b27a3185a7a704a
Source dataset
uspto-grants-1989_03
Patent number
US04810792

Reaction notes

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