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 1594582Notes

Reaction equation

HRID 1594582 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-fluorophenoxy)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 hours. 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 calc'd for C18H21ClFN4O (MH+): 363.1388, found: 363.1384.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 16 hours
  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-f359240ff003451bbf632a577c750a0f
Source dataset
uspto-grants-2001_09
Patent number
US06284757B1

Reaction notes

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