Sodium hydride → HCID 86672285, compound

HRID 2359814Notes

Reaction equation

HRID 2359814 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]1[N:16]=[C:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:14]=[CH:13][CH:12]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].[Cl-].[NH4+]>CN(C)C=O.O>[C:27]([O:26][C:24](=[O:25])[CH2:23][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:5])[CH3:4])=[O:9])[C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[N:16]=1)([CH3:30])([CH3:29])[CH3:28]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 79177tert-Butyl bromoacetateHCID 19349079Ethyl 6-[(tert-butoxycarbonyl)amino]pyridine-2-carboxylate

Product 1

HCID 86672285HCID 86672285, compoundYield 93.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of sodium hydride (mineral oil 55% dispersion) (15.7 g, 0.360 mol) in N,N-dimethylformamide (362 ml) was added dropwise a solution of ethyl 6-tert-butoxycarbonylaminopyridin-2-carboxylate (see WO 2006/074884A) (81.2 g, 0.305 mol) in N,N-dimethylformamide (300 ml) over 20 minutes under ice cooling in an argon atmosphere, followed by stirring at room temperature for 1 hour. tert-Butyl bromoacetate (54.0 ml, 0.366 mol) was then added dropwise over 10 minutes under ice cooling, followed by further stirring at room temperature for 1 hour. After completion of the reaction, to the reaction solution was added an aqueous solution in which ammonium chloride (1.77 g, 33.0 mmol) was dissolved in water (300 ml), followed by extraction with toluene. The separated organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent; hexane:ethyl acetate=9:1→4:1 (V/V)), and fractions containing the desired compound were concentrated under reduced pressure to afford the title compound (108 g) as a pale yellow liquid. (Yield: 93%)

Workup

  1. stirringby further stirring at room temperature for 1 hour
  2. customAfter completion of the reaction
  3. extractionfollowed by extraction with toluene
  4. washThe separated organic layer was washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additioncontaining the desired compound
  8. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-bd7bdf254f1347b68bb33f5d65165fc0
Source dataset
uspto-grants-2014_04
Patent number
US08685986B2

Reaction notes

Loading…