Sodium Carbonate → (7S,8aS)-7-(4-Fluorophenoxy)methyl-2-(6-chloropyridazin-3-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

HRID 861357Notes

Reaction equation

HRID 861357 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][CH2:7][CH:8]2[CH2:16][N:11]3[CH2:12][CH2:13][NH:14][CH2:15][CH:10]3[CH2:9]2)=[CH:4][CH:3]=1.[Cl:19][C:20]1[N:21]=[N:22][C:23](Cl)=[CH:24][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC(C)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][C@@H:8]2[CH2:16][N:11]3[CH2:12][CH2:13][N:14]([C:23]4[N:22]=[N:21][C:20]([Cl:19])=[CH:25][CH:24]=4)[CH2:15][C@@H:10]3[CH2:9]2)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 673313,6-DichloropyridazineHCID 20682345(7RS,8aSR)-7-(4-fluorophenoxy)methyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

Product 1

HCID 86752025(7S,8aS)-7-(4-Fluorophenoxy)methyl-2-(6-chloropyridazin-3-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 66%

Reagents, catalysts & solvents 1

HCID 31260Isoamyl AlcoholSolvent

Procedure

A mixture of 0.500 g (2.00 mmol) of (7SR,8aSR)-7-(4-fluoro-phenoxy)methyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 3), 1.49 g (10.0 mmol) of 3,6-dichloropyridazine, and 0.508 g (4.79 mmol) of sodium carbonate in 50 mL of isoamyl alcohol was heated to reflux for 48 h. The reaction was cooled to ambient temperature, the solvent removed in vacuo, the residue taken up in ethyl acetate and water, the pH was adjusted to 11 with sodium carbonate and the layers were separated. The aqueous phase was extracted with ethyl acetate, and the combined organic layers were dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with 90:10 ethyl acetate:hexane gave 0.478 g (66%) of the title compound. mp (.HCl) 229° C. (dec). HRMS calcd for C18 H21ClFN4O (MH+): 363.1388, found: 363.1404.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 48 h
  3. customthe solvent removed in vacuo
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted with ethyl acetate
  6. dry with materialthe combined organic layers were dried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by flash silica gel chromatography with 90:10 ethyl acetate

Sources & evidence

ORD record
ord-b388b9834bec43e7b3f5836fde78d358
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

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