Phosphorus oxychloride → HCID 23288944, compound

HRID 1417832Notes

Reaction equation

HRID 1417832 reaction equation
[CH:1]1([CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([NH2:26])=O)=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O>CN(C)C=O>[CH:1]1([CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:19]=[CH:20][C:21]([C:24]#[N:26])=[CH:22][CH:23]=3)[CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 23288849HCID 23288849, compound

Product 1

HCID 23288944HCID 23288944, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-[2-(indan-1-yl)ethyl]-1-(4-carboxamido)phenylpiperazine (CXII, EXAMPLE 77, 0.7 g, 2 mmol), phosphorus oxychloride (0.93 ml, 10 mmol) in dimethylformamide (20 ml) is heated at 80° for 2 hr. The mixture is stirred for 2 hr and quenched with sodium hydroxide (20%) until the pH>13. The mixture is extracted with ethyl acetate (800 ml), and the organic phase is washed with saline, dried (magnesium sulfate), filtered and concentrated. The concentrate is purified by liquid chromatography on silica gel 60 (400 g), eluting with hexane/ethyl acetate (1/1). The appropriate fractions homogeneous by TLC are combined and concentrated to give the free base of title compound, which is converted into the hydrochloric acid salt and crystallized from hexane/ethyl acetate to give the title compound, mp 157°-158°, NMR (CDCl6, TMS) 7.62-6.92 and 3.94-1.46 δ.

Workup

  1. temperatureis heated at 80° for 2 hr
  2. customquenched with sodium hydroxide (20%) until the pH>13
  3. extractionThe mixture is extracted with ethyl acetate (800 ml)
  4. washthe organic phase is washed with saline
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe concentrate is purified by liquid chromatography on silica gel 60 (400 g)
  9. washeluting with hexane/ethyl acetate (1/1)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-cb319d7d9e3c4ff5b44e7879f41fc4de
Source dataset
uspto-grants-1999_03
Patent number
US05877317

Reaction notes

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