Sodium hydride → HCID 44464434, compound

HRID 453270Notes

Reaction equation

HRID 453270 reaction equation
[OH:1][C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][C:12]([O:18][CH3:19])=[CH:13][CH:14]=3)[CH:9]=2)[N:3]=1.[H-].[Na+].Cl[CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>CN(C)C=O>[CH3:19][O:18][C:12]1[CH:11]=[C:10]2[C:15]([CH:16]=[CH:17][C:8]([N:4]3[C:5]([CH3:7])=[CH:6][C:2]([O:1][CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[N:3]3)=[CH:9]2)=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 767274-(2-Chloroethyl)morpholineHCID 178487479HCID 178487479, compound

Product 1

HCID 44464434HCID 44464434, compoundYield 81.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 3-hydroxy-5-methyl-1-(7-methoxynaphthalen-2-yl)-1H-pyrazol (1.51 g, 5.96 mmol) in dimethylformamide (40 ml), cooled down to 0° C., a dispersion in mineral oil at 60% of NaH (0.36 g, 8.94 mmol) was added, the cooling bath was removed, and was left to stirring until it recovered the room temperature (1.5 hrs). Subsequently, 2-chloroethylmorpholine (1.02 g, 6.85 mmol) dissolved in DMF (10 ml) was added dropwise, and the resulting mixture was heated at 60° C. during 20 hrs. Water-ice was added and it was evaporated to dryness in a rotavapor. The resulting slurry was divided between water and ethyl ether. The aqueous phase was newly extracted with a solvent, and the collection of organic phases was washed with water, dried over sodium sulfate, filtered, and evaporated yielding 2.19 g of a crude product, which was purified by crystallization of its chlorhydrate (prepared by dissolving in HCl-saturated dioxane) in isopropyl alcohol-ethyl ether. 1.78 g (74%) of the 4-{2-[1-(7-methoxynaphthalen-2-yl)-5-methyl-1H-pyrazol-3-yloxy]ethyl}morpholine chlorhydrate were obtained as a solid with a m.p.=143-147° C.

Workup

  1. customthe cooling bath was removed
  2. waitwas left
  3. customrecovered the room temperature (1.5 hrs)
  4. additionwas added dropwise
  5. customit was evaporated to dryness in a rotavapor
  6. extractionThe aqueous phase was newly extracted with a solvent
  7. customthe collection of organic phases
  8. washwas washed with water
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customyielding 2.19 g of a crude product, which
  13. customwas purified by crystallization of its chlorhydrate (prepared by dissolving in HCl-saturated dioxane) in isopropyl alcohol-ethyl ether

Sources & evidence

ORD record
ord-5b93e41143664789bcd490f7b87ade73
Source dataset
uspto-grants-2013_07
Patent number
US08492425B2

Reaction notes

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