Sodium hydride → Tert-butyl 3-[(5-carbamoyl-6-chloro-3-ethylpyrazin-2-yl)oxy]pyrrolidine-1-carboxylate

HRID 1526188Notes

Reaction equation

HRID 1526188 reaction equation
[OH:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[H-].[Na+].[Cl:16][C:17]1[C:18]([C:26]([NH2:28])=[O:27])=[N:19][C:20]([CH2:24][CH3:25])=[C:21](Cl)[N:22]=1>CN(C)C=O>[C:26]([C:18]1[N:19]=[C:20]([CH2:24][CH3:25])[C:21]([O:1][CH:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)=[N:22][C:17]=1[Cl:16])(=[O:27])[NH2:28]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 44169391-Boc-3-pyrrolidinolHCID 848199603,5-Dichloro-6-ethylpyrazine-2-carboxamide

Product 1

HCID 117666931Tert-butyl 3-[(5-carbamoyl-6-chloro-3-ethylpyrazin-2-yl)oxy]pyrrolidine-1-carboxylateYield 40.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1 g) and N,N-dimethylformamide (30 mL) was added 55% oily sodium hydride (233 mg) under ice-cooling. After stirring for 30 minutes under ice-cooling, 3,5-dichloro-6-ethylpyrazine-2-carboxamide (1.18 g) was added thereto, followed by further stirring for 1 hour under ice-cooling. The reaction mixture was poured into ice water, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: chloroform) to obtain tert-butyl 3-[(5-carbamoyl-6-chloro-3-ethylpyrazin-2-yl)oxy]pyrrolidine-1-carboxylate (795 mg) as a pale yellow solid.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringby further stirring for 1 hour under ice-
  4. temperaturecooling
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe organic phase was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (eluent: chloroform)

Sources & evidence

ORD record
ord-a9f709766b0641feb081ab59c487c756
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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