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

HRID 861352Notes

Reaction equation

HRID 861352 reaction equation
[OH:1][C@@H:2]1[CH2:17][N:5]2[CH2:6][CH2:7][N:8]([C:10]3[N:15]=[CH:14][C:13]([F:16])=[CH:12][N:11]=3)[CH2:9][C@@H:4]2[CH2:3]1.[H-].[Na+].[C:20]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25]Br)#[N:21]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:20]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25][O:1][C@@H:2]1[CH2:17][N:5]2[CH2:6][CH2:7][N:8]([C:10]3[N:11]=[CH:12][C:13]([F:16])=[CH:14][N:15]=3)[CH2:9][C@@H:4]2[CH2:3]1)#[N:21]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 97249Benzonitrile, 3-(bromomethyl)-HCID 15886075(7S,8aS)-7-Hydroxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

Product 1

HCID 15886069(7S,8aS)-7-(3-Cyanobenzyl)oxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 12.5%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 0.60 g (2.5 mmol) of (7S,8aS)-7-hydroxy-2-(5-fluoropyrimidin -2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]-pyrazine (Preparation 15) in 30 mL of THF was treated with 0.41 g (10 mmol) of sodium hydride (60% oil dispersion), followed by 0.75 g (3.8 mmol) of 3-cyanobenzyl bromide and 30 mg (0.1 mmol) of tetra-n-butylammonium iodide. The mixture was stirred 50° C. for 16 h, cooled to room temperature, the solvent was evaporated, and the residue partitioned between ethyl acetate and water. The layers were separated, the organic phase was washed with water and brine, dried (magnesium sulfate), filtered and evaporated. Purification by MPLC silica gel chromatography with ethyl acetate gave 0.11 g (12%) of the title compound. mp (.HCl) 95°-100° C. HRMS calcd for C19H21FN5O (MH+): 345.1730; found: 345.1739.

Workup

  1. temperaturecooled to room temperature
  2. customthe solvent was evaporated
  3. customthe residue partitioned between ethyl acetate and water
  4. customThe layers were separated
  5. washthe organic phase was washed with water and brine
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by MPLC silica gel chromatography with ethyl acetate

Sources & evidence

ORD record
ord-7e4726b43ce148609471182f3edc653f
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

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