Sodium hydride → (7R,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 861343Notes

Reaction equation

HRID 861343 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.[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Br)=[CH:21][CH:20]=1.[H-].[Na+]>CN(C=O)C.O>[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][O:1][C@H:2]2[CH2:17][N:5]3[CH2:6][CH2:7][N:8]([C:10]4[N:11]=[CH:12][C:13]([F:16])=[CH:14][N:15]=4)[CH2:9][C@@H:4]3[CH2:3]2)=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 15886074(7R,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 70245864(7R,8aS)-7-(4-Fluorobenzyl)oxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 8.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 0.75 g (3.15 mmol) of (7R,8aS)-7-hydroxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 6) and 0.79 mL (6.3 mmol) of 4-fluorobenzyl bromide in 30 mL of dry DMF was treated with 0.15 g (3.8 mmol) of sodium hydride (60% oil dispersion), and the mixture was heated at 100° C. for 18 h. The mixture was cool, diluted with water, and extracted with diethyl ether (5×). The combined organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatograph with 50:50 ethyl acetate:hexane gave 0.090 g (8%) of the title compound. mp (.HCl) 74°-79° C. 13C NMR (base, CDCl3): δ 35.6, 43.9, 48.9, 51.2, 60.4, 60.7, 70.7, 76.7, 115.1, 115.4, 129.35, 129.46, 133.9, 144.9, 145.2, 149.9, 153.2, 158.9, 164.0. HRMS calcd for C18H20F2N4O (MH+): 347.1683, found: 347.1671.

Workup

  1. temperatureThe mixture was cool
  2. extractionextracted with diethyl ether (5×)
  3. dry with materialThe combined organic phase was dried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. customPurification by flash silica gel chromatograph with 50:50 ethyl acetate

Sources & evidence

ORD record
ord-d85ffac8773d4ea5a0b29bfd40532b0d
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

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