Sodium Carbonate → (7R,8aS)-7-hydroxy-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

HRID 1594599Notes

Reaction equation

HRID 1594599 reaction equation
[OH:1][C@H:2]1[CH2:10][N:5]2[CH2:6][CH2:7][NH:8][CH2:9][C@@H:4]2[CH2:3]1.Cl[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][N:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC(C)C>[OH:1][C@H:2]1[CH2:10][N:5]2[CH2:6][CH2:7][N:8]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][N:13]=3)[CH2:9][C@@H:4]2[CH2:3]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 276852,5-DichloropyridineHCID 53338751(7R,8aS)-octahydropyrrolo[1,2-a]piperazin-7-ol

Product 1

HCID 15886072(7R,8aS)-7-hydroxy-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 9.3%

Reagents, catalysts & solvents 1

HCID 31260Isoamyl AlcoholSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3.81 g (26.8 mmol) of (7R,8aS)-7-hydroxy-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 6, Step A), 19.8 g (134 mmol) of 2,5-dichloropyridine, 7.10 g (67.0 mmol) of sodium carbonate and 275 mL of isoamyl alcohol was heated at reflux for 72 hours. The mixture was cooled to about 100° C., filtered hot, and the filtrate concentrated in vacuo. Purification of the residue by flash silica gel chromatography with 9:1 chloroform:methanol gave 0.63 g (9%) of the title compound of sufficient purity for use in subsequent reactions. m/z (MH+) 254.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 72 hours
  3. filtrationfiltered hot
  4. concentrationthe filtrate concentrated in vacuo
  5. customPurification of the residue by flash silica gel chromatography with 9:1 chloroform

Sources & evidence

ORD record
ord-e7bbaedc9aad4808b8e60cb6ada29616
Source dataset
uspto-grants-2001_09
Patent number
US06284757B1

Reaction notes

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