Piperazine → 1-(6-Methoxypyridin-2-yl)piperazine

HRID 326499

Reaction equation

HRID 326499 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[N:3]=1.[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.C(=O)([O-])[O-].[K+].[K+]>O>[N:10]1([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[N:3]=2)[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 4837PiperazineHCID 11430Potassium CarbonateHCID 870092-Chloro-6-methoxypyridine

Product 1

HCID 122004701-(6-Methoxypyridin-2-yl)piperazine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2-chloro-6-methoxypyridine (20 g) and piperazine (32.9 g) with potassium carbonate (20.1 g) in water (50 ml) is stirred at 100° for 24 hr. The mixture is partitioned between methylene chloride and aqueous sodium bicarbonate, the phases are separated and the organic phase is dried over sodium sulfate and concentrated. The concentrate is dissolved in ether. The organic phase is extracted with hydrochloric acid (10%). The aqueous phase is washed with ether, neutralized with sodium hydroxide (10%) and extracted with methylene chloride. The organic phase is dried over sodium sulfate and concentrated to give 2-piperazino-6-methoxypyridine. This material is stirred in acetonitrile (100 ml) with 21-bromo-17α-hydroxypregna-4,9(11)-diene-3,20-dione (3.01 g) and potassium carbonate (1.3 g) at 20°-25° for 16 hr. The mixture is partitioned between methylene chloride and aqueous sodium bicarbonate. The phases are separated and the organic phase is dried over sodium sulfate and concentrated. The concentrate is chromatographed over silica gel (2% methanol in methylene chloride to 4%) to give the free base of the title compound which is 92% pure by HPLC. This material is dissolved in ethyl acetate and treated with methane sulfonic acid (0.606 g). The salt is filtered and recrystallized from methanol and ethyl acetate to give the title compound.

Workup

  1. customThe mixture is partitioned between methylene chloride and aqueous sodium bicarbonate
  2. customthe phases are separated
  3. dry with materialthe organic phase is dried over sodium sulfate
  4. concentrationconcentrated
  5. dissolutionThe concentrate is dissolved in ether
  6. extractionThe organic phase is extracted with hydrochloric acid (10%)
  7. washThe aqueous phase is washed with ether
  8. extractionextracted with methylene chloride
  9. dry with materialThe organic phase is dried over sodium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-a6297edcf4854fa8889cc1391168be9c
Source dataset
uspto-grants-1993_12
Patent number
US05268477

Linked notes

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