Phosphoric Acid → 1-[3-(1,1-Dimethylethylamino)pyridyl]piperazine

HRID 2395743Notes

Reaction equation

HRID 2395743 reaction equation
[CH3:1][C:2](=[CH2:4])[CH3:3].CC(C)(OC([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[C:22]([NH2:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:13][CH2:12]1)=O)C.P(=O)(O)(O)O.B(F)(F)F.CCOCC>C(Cl)Cl>[CH3:4][C:2]([NH:23][C:22]1[C:17]([N:14]2[CH2:13][CH2:12][NH:11][CH2:16][CH2:15]2)=[N:18][CH:19]=[CH:20][CH:21]=1)([CH3:3])[CH3:1]

Participants

6

Reactant 4

HCID 1004Phosphoric AcidHCID 8000Boron trifluoride etherateHCID 8255Isobutylene2×HCID 2756375tert-Butyl 4-(3-aminopyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 110426831-[3-(1,1-Dimethylethylamino)pyridyl]piperazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Isobutylene (10 ml) is condensed into a solution of 1-[1,1-dimethylethoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine (International Publication No. WO 88/08424, 200 mg) in methylene chloride (10 ml) at -70°. Phosphoric acid (85%, 50 μl) is added and the mixture stirred for 60 minutes. Boron trifluoride etherate (200 μl) is added dropwise and the resulting suspension is stirred 8 hours at reflux and overnight at 20°-25° allowing the isobutylene to evaporate. The suspension is diluted with water and ammonium hydroxide is added until basic to pH paper and then extracted with methylene chloride (3 ×). The combined extracts are dried over anhydrous potassium carbonate, filtered, and concentrated under reduced pressure to a liquid which is flash chromatographed (silica gel, 230-400 mesh), eluting with methanol/chloroform (3/20). The appropriate fractions are pooled and concentrated to give an oil. The NMR, CMR, IR, and MS (m/e) M+234 support the title compound.

Workup

  1. stirringthe resulting suspension is stirred 8 hours
  2. temperatureat reflux and overnight at 20°-25°
  3. customto evaporate
  4. additionThe suspension is diluted with water and ammonium hydroxide
  5. additionis added until basic
  6. extractionextracted with methylene chloride (3 ×)
  7. dry with materialThe combined extracts are dried over anhydrous potassium carbonate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure to a liquid which
  10. customchromatographed (silica gel, 230-400 mesh)
  11. washeluting with methanol/chloroform (3/20)
  12. concentrationconcentrated
  13. customto give an oil

Sources & evidence

ORD record
ord-018b339dcfa24b7e9115828dc43d6d41
Source dataset
uspto-grants-1996_02
Patent number
US05489593

Reaction notes

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