Sodium hydride → HCID 21906088, compound

HRID 1926643Notes

Reaction equation

HRID 1926643 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].[H][H].[Cl:19][C:20]1[CH:25]=[N:24][CH:23]=[C:22](Cl)[N:21]=1>CN(C=O)C>[Cl:19][C:20]1[N:21]=[C:22]([O:14][CH:11]2[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]2)[CH:23]=[N:24][CH:25]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 785042,6-DichloropyrazineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 21906088HCID 21906088, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1-boc-4-hydroxypiperidine (3.80 g, 18.9 mmol) in DMF (76 mL) at 0° C. was added sodium hydride (60% mineral oil dispersion; 0.906 g, 22.7 mmol). Once hydrogen evolution had ceased, 2,6-dichloropyrazine (2.81 g, 18.9 mmol) was added and the reaction mixture was allowed to warm to ambient temperature. After 1 h, the reaction mixture was quenched with brine (100 mL) and extracted with EtOAc (2×100 mL). The combined organics were dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford tert-butyl 4-[(6-chloropyrazin-2-yl)oxy]piperidine-1-carboxylate as a yellow solid. LRMS (ESI) calculated for C14H20ClN3O3 336.1; found [M+Na]+, 336.1.

Workup

  1. customthe reaction mixture was quenched with brine (100 mL)
  2. extractionextracted with EtOAc (2×100 mL)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-0e2d26ceb921498eac81d82cc1d1e9ba
Source dataset
uspto-grants-2012_05
Patent number
US08183245B2

Reaction notes

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