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

HRID 861344Notes

Reaction equation

HRID 861344 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.[H-].[Na+].CS(O[C@H:17]1[CH2:32][N:20]2[CH2:21][CH2:22][N:23]([C:25]3[N:30]=[CH:29][C:28]([F:31])=[CH:27][N:26]=3)[CH2:24][C@@H:19]2[CH2:18]1)(=O)=O>CN(C=O)C.O>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][O:7][C@@H:17]2[CH2:32][N:20]3[CH2:21][CH2:22][N:23]([C:25]4[N:26]=[CH:27][C:28]([F:31])=[CH:29][N:30]=4)[CH2:24][C@@H:19]3[CH2:18]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 680224-Fluorobenzylic alcoholHCID 86752023(7R,8aS)-7-methanesulfonyloxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

Product 1

HCID 15886067(7S,8aS)-7-(4-Fluorobenzyl)oxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 20%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of 1.15 mL (10.2 mmol) of 4-fluorobenzyl alcohol in 35 mL of dry DMF was treated with 0.48 g (12 mmol) of sodium hydride (60% oil dispersion), and the mixture was stirred at 50° C. for 30 min. A solution of 1.15 g (3.64 mmol) of (7R,8aS)-7-methanesulfonyloxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 7) in 35 mL of dry DMF was added and the solution stirred at 100° C. for 18 h. The solution was cooled, diluted with water, and extracted with diethyl ether (2×). The combined organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with ethyl acetate gave 0.25 g (20%) of the title compound. mp (.D-(-)-tartrate) 76°-81° C. 13C NMR (base, CDCl3): δ 36.3, 43.6, 48.8, 51.3, 60.2, 61.9, 70.4, 76.6, 115.0, 115.3, 129.43, 129.53, 134.0, 144.9, 145.2, 149.9, 153.2, 158.9, 160.6, 163.9. HRMS calcd for C18H20F2N4O (MH+): 347.1683, found: 347.1706.

Workup

  1. stirringthe solution stirred at 100° C. for 18 h
  2. temperatureThe solution was cooled
  3. extractionextracted with diethyl ether (2×)
  4. dry with materialThe combined organic phase was dried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by flash silica gel chromatography with ethyl acetate

Sources & evidence

ORD record
ord-1a23a273d1f34d00860f115313444cec
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

Loading…