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

HRID 1594590Notes

Reaction equation

HRID 1594590 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[N:17]=[CH:16][C:15]([F:18])=[CH:14][N:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>O>[OH:1][C@H:2]1[CH2:10][N:5]2[CH2:6][CH2:7][N:8]([C:12]3[N:17]=[CH:16][C:15]([F:18])=[CH:14][N:13]=3)[CH2:9][C@@H:4]2[CH2:3]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 5834662-Chloro-5-fluoropyrimidineHCID 53338751(7R,8aS)-octahydropyrrolo[1,2-a]piperazin-7-ol

Product 1

HCID 15886074(7R,8aS)-7-hydroxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 85%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of the crude (7R,8aS)-7-hydroxy-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]-pyrazine, 9.96 g (52.5 mmol) of 2-chloro-5-fluoropyrimidine (Dunaiskis, A. et al., Org. Prep. Proc. Int., 1995, 27, 600-602), 13.4 g (126 mmol) of sodium carbonate and 450 mL of water was heated at 95° C. for 72 hours. The mixture was cooled, extracted with chloroform (2×), and the combined organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with 95:5 ethyl acetate:methanol gave 8.54 g (85%) of the title compound. 13C NMR (base, CDCl3): δ 39.1, 43.7, 48.7, 51.0, 60.2, 62.9, 69.4, 144.95, 145.24, 149.9, 153.2,158.9. m/z (MH+) 239.

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with chloroform (2×)
  3. dry with materialthe combined organic phase was dried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. customPurification by flash silica gel chromatography with 95:5 ethyl acetate

Sources & evidence

ORD record
ord-4a2195d0781c42fe98011bd90e3ba143
Source dataset
uspto-grants-2001_09
Patent number
US06284757B1

Reaction notes

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