Sodium Carbonate → (7RS,9aSR)-7-hydroxymethyl-2-(3,5-dichloropyridin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine

HRID 1977019Notes

Reaction equation

HRID 1977019 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:12][N:7]2[CH2:8][CH2:9][NH:10][CH2:11][CH:6]2[CH2:5][CH2:4]1.Cl[C:14]1[C:19]([Cl:20])=[CH:18][C:17]([Cl:21])=[CH:16][N:15]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC(C)C>[OH:1][CH2:2][CH:3]1[CH2:12][N:7]2[CH2:8][CH2:9][N:10]([C:14]3[C:19]([Cl:20])=[CH:18][C:17]([Cl:21])=[CH:16][N:15]=3)[CH2:11][CH:6]2[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27666Pyridine, 2,3,5-trichloro-HCID 12985539(Octahydro-1H-pyrido[1,2-A]pyrazin-7-YL)methanol

Product 1

HCID 69431843(7RS,9aSR)-7-hydroxymethyl-2-(3,5-dichloropyridin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazineYield 80%

Reagents, catalysts & solvents 1

HCID 31260Isoamyl AlcoholSolvent

Procedure

A mixture of 0.75 g (4.4 mmol) of (7RS,9aSR)-7-hydroxymethyl-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine, 4.02 g (22.1 mmol) of 2,3,5-trichloropyridine, 1.12 g (10.6 mmol) of sodium carbonate and 30 mL of isoamylalcohol was refluxed for 72 h. The mixture was cooled to room temperature, filtered, and concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with saturated sodium carbonate. The organic layer was dried (magnesium sulfate), filtered and evaporated, and the crude product was purified by flash chromatography on silica gel eluting with 95:5 chloroform:methanol to give 1.10 g (80%) of (7RS,9aSR)-7-hydroxymethyl-2-(3,5-dichloro-pyridin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine.

Workup

  1. temperaturewas refluxed for 72 h
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with saturated sodium carbonate
  6. dry with materialThe organic layer was dried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. customthe crude product was purified by flash chromatography on silica gel eluting with 95:5 chloroform

Sources & evidence

ORD record
ord-fea4d25e3a84488ba9c4c6bb1b330975
Source dataset
uspto-grants-2001_05
Patent number
US06231833B1

Reaction notes

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