Sodium hydride → HCID 57951062, compound

HRID 530945Notes

Reaction equation

HRID 530945 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[H-].[Na+].Cl[C:21]1[N:22]=[CH:23][C:24]([C:27]([O:29][CH3:30])=[O:28])=[N:25][CH:26]=1>CN(C)C=O>[F:17][C:2]([F:1])([F:16])[C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([O:15][C:21]3[N:22]=[CH:23][C:24]([C:27]([O:29][CH3:30])=[O:28])=[N:25][CH:26]=3)[CH2:11][CH2:10]2)=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 220976741-[4-(Trifluoromethyl)phenyl]piperidin-4-ol

Product 1

HCID 57951062HCID 57951062, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

1-(4-(Trifluoromethyl)phenyl)piperidin-4-ol (0.59 g, 2.41 mmol) was dissolved in anhydrous N,N-dimethylformamide (10 mL), cooled in an ice bath and treated with 60% sodium hydride (0.1 g, 2.55 mmol). The mixture was allowed to warm to room temperature over 1 h. A solution of methyl 5-chloropyrazine-2-carboxylate (0.5 g, 2.9 mmol) in anhydrous N,N-dimethylformamide (1 mL) was added and the mixture was stirred at room temperature overnight. The mixture was quenched by water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and evaporated. The residue obtained was purified by flash chromatography (silica gel, ethyl acetate/hexanes=1/4) to afford methyl 5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)pyrazine-2-carboxylate as a white solid (0.23 g, 25%). 1H-NMR (CD3Cl, 300 MHz): δ 8.86 (m, 1H), 8.28 (m, 1H), 7.48 (m, 2H), 6.96 (m, 2H), 5.36 (m, 1H), 4.00 (s, 3H), 3.64 (m, 2H), 3.26 (m, 2H), 2.16 (m, 2H), 1.99 (m, 2H) ppm; MS (ESI): 382.6 (M+1).

Workup

  1. temperaturecooled in an ice bath
  2. customThe mixture was quenched by water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customevaporated
  6. customThe residue obtained
  7. customwas purified by flash chromatography (silica gel, ethyl acetate/hexanes=1/4)

Sources & evidence

ORD record
ord-4a64051da0f84a9d8ccfeeee57d2aa2f
Source dataset
uspto-grants-2016_05
Patent number
US09353111B2

Reaction notes

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