Sodium Carbonate → (7RS,8aSR)-7-(4-Fluorophenoxy)methyl-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

HRID 861340Notes

Reaction equation

HRID 861340 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[F:15][C:16]1[CH:32]=[CH:31][C:19]([O:20][CH2:21][CH:22]2[CH2:30][N:25]3[CH2:26][CH2:27][NH:28][CH2:29][CH:24]3[CH2:23]2)=[CH:18][CH:17]=1>C(O)CC(C)C>[F:15][C:16]1[CH:17]=[CH:18][C:19]([O:20][CH2:21][CH:22]2[CH2:30][N:25]3[CH2:26][CH2:27][N:28]([C:2]4[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=4)[CH2:29][CH:24]3[CH2:23]2)=[CH:31][CH:32]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 276852,5-DichloropyridineHCID 20682345(7RS,8aSR)-7-(4-fluorophenoxy)methyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

Product 1

HCID 9841887(7RS,8aSR)-7-(4-Fluorophenoxy)methyl-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 2%

Reagents, catalysts & solvents 1

HCID 31260Isoamyl AlcoholSolvent

Procedure

A mixture of 3.8 g (26 mmol) of 2,5-dichloropyridine, 1.3 g (12 mmol) of sodium carbonate, 1.3 g (5.2 mmol) of (7RS,8aSR)-7-(4-fluorophenoxy)methyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 2), and 20 mL of isoamyl alcohol was heated at reflux for 18 h. The solvent was evaporated, the residue taken up in water and ethyl acetate, and the pH adjusted to 11 with sodium carbonate. The layers were separated and the organic phase was dried (magnesium sulfate), filtered, and evaporated. Purification by medium pressure silica gel chromatography with ethyl acetate gave 35 mg (2%) of the title compound. mp (.HCl) 202°-206° C. HRMS calcd for C19H21 ClFN3O (MH+): 362.1435, found: 362.1451.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 h
  3. customThe solvent was evaporated
  4. customThe layers were separated
  5. dry with materialthe organic phase was dried (magnesium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by medium pressure silica gel chromatography with ethyl acetate

Sources & evidence

ORD record
ord-e30d90d564d642e5a4156f87da53c4e3
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

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