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

HRID 861351Notes

Reaction equation

HRID 861351 reaction equation
[OH:1][C@@H:2]1[CH2:17][N:5]2[CH2:6][CH2:7][N:8]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=3)[CH2:9][C@@H:4]2[CH2:3]1.[H-].[Na+].[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][O:1][C@@H:2]2[CH2:17][N:5]3[CH2:6][CH2:7][N:8]([C:10]4[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=4)[CH2:9][C@@H:4]3[CH2:3]2)=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 15886073(7S,8aS)-7-hydroxy-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

Product 1

HCID 15886060(7S,8aS)-7-(4-Fluorobenzyl)oxy-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 41%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.23 g (0.91 mmol) of (7S,8aS)-7-hydroxy-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 18) in 10 mL of dry THF was treated with 40 mg (1.0 mmol) of sodium hydride (60% oil dispersion), followed by 0.125 mL (1.0 mmol) of 4-fluorobenzyl bromide and 17 mg (0.05 mmol) of tetra-n-butylammonium iodide. The mixture was stirred at ambient temperature for 16 h, and warmed to 50° C. for 4 h. The suspension was cooled, the solvent was evaporated, and the residue partitioned between ethyl acetate and water. The layers were separated, and the organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with 95:5 chloroform: methanol gave 0.135 g (41%) of the title compound. mp (.HCl) 165°-168° C. HRMS calcd for C19H22ClFN3O (MH+): 362.1435, found: 362.1451.

Workup

  1. temperaturewarmed to 50° C. for 4 h
  2. temperatureThe suspension was cooled
  3. customthe solvent was evaporated
  4. customthe residue partitioned between ethyl acetate and water
  5. customThe layers were separated
  6. dry with materialthe organic phase was dried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by flash silica gel chromatography with 95:5 chloroform

Sources & evidence

ORD record
ord-20734baf7cab410d85bff1317018a45b
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

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