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

HRID 861356Notes

Reaction equation

HRID 861356 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[CH:25]=[N:24][CH:23]=[C:22](Cl)[N:21]=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:22]4[CH:23]=[N:24][CH:25]=[C:20]([Cl:19])[N:21]=4)[CH2:15][C@@H:10]3[CH2:9]2)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 785042,6-DichloropyrazineHCID 20682345(7RS,8aSR)-7-(4-fluorophenoxy)methyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

Product 1

HCID 86752024(7S,8aS)-7-(4-Fluorophenoxy)methyl-2-(6-chloropyrazin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 68%

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 2,6-dichloropyrazine, and 0.508 g (4.79 mmol) of sodium carbonate in 50 mL of isoamyl alcohol was heated to reflux for 16 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 0.491 g (68%) of the title compound. mp (.HCl) 209°-212° C. HRMS calcd for C18H21ClFN4O (MH+): 363.1388, found: 363.1384.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 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-4ed936f7cfd04f7dac10c7a2477c6fd0
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

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