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

HRID 1594596Notes

Reaction equation

HRID 1594596 reaction equation
[OH:1][CH2:2][C@@H:3]1[CH2:11][N:6]2[CH2:7][CH2:8][NH:9][CH2:10][C@@H:5]2[CH2:4]1.Cl[C:13]1[N:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>O>[OH:1][CH2:2][C@@H:3]1[CH2:11][N:6]2[CH2:7][CH2:8][N:9]([C:13]3[N:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=3)[CH2:10][C@@H:5]2[CH2:4]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 5834662-Chloro-5-fluoropyrimidineHCID 45099445HCID 45099445, compound

Product 1

HCID 15886071(7S,8aS)-7-hydroxymethyl-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 43.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 1.38 g (8.84 mmol) of (7S,8aS)-7-hydroxymethyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine, 1.30 g (9.87 mmol) of 2-chloro-5-fluoropyrimidine (Dunaiskis, A. et al., Org. Prep. Proc. Int., 1995, 27, 600-602), and 2.85 g (26.9 mmol) of sodium carbonate and 90 mL of water was heated at 95° C. for 16 hours. The solution was cooled and extracted with chloroform (2×), the combined organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with 9:1 chloroform:methanol gave 0.97 g (43%) of the title compound. Mp 123-124° C. m/z (MH+) 253. 13C NMR (CDCl3): δ 30.9, 37.1, 43.8, 48.8, 51.3, 57.5, 62.6, 67.2, 144.9, 145.2, 149.9, 153.2, 158.8.

Workup

  1. temperatureThe solution 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 9:1 chloroform

Sources & evidence

ORD record
ord-b60a941b82de438287ffd590cd317489
Source dataset
uspto-grants-2001_09
Patent number
US06284757B1

Reaction notes

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