Sodium hydride → HCID 58001769, compound

HRID 420680Notes

Reaction equation

HRID 420680 reaction equation
[CH3:1][C:2]1([CH3:24])[O:7][CH2:6][CH:5]([NH:8][C:9]2[C:14]([NH:15][CH2:16][C:17](OCC)=[O:18])=[CH:13][CH:12]=[C:11]([O:22][CH3:23])[N:10]=2)[CH2:4][O:3]1.[H-].[Na+].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[CH3:1][C:2]1([CH3:24])[O:7][CH2:6][CH:5]([N:8]2[C:17](=[O:18])[CH2:16][NH:15][C:14]3[CH:13]=[CH:12][C:11]([O:22][CH3:23])=[N:10][C:9]2=3)[CH2:4][O:3]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 58001797HCID 58001797, compound

Product 1

HCID 58001769HCID 58001769, compoundYield 82.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

Ethyl N-[2-[(2,2-dimethyl-1,3-dioxan-5-yl)amino]-6-(methyloxy)-3-pyridinyl]glycinate (35.42 g, 104.4 mmol) was dissolved in dry THF (500 ml) and the solution was added dropwise over 2 h to a cooled (0° C.) suspension of sodium hydride (4.173 g of 60% w:w dispersion in oil) in dry THF (500 ml) under argon. During the addition the colour of the suspension changed from orange to green. The mixture was stirred at 0° C. for a further 15 minutes, then allowed to warm to room temperature and stirred at rt for 1 h. The mixture was cooled to 0° C. and saturated NH4Cl (15 ml) was added cautiously with vigorous stirring (effervescence observed). After effervescence had ceased, the mixture was allowed to warm to room temperature and stirred for 4 h then diluted with EtOAc (500 ml) and filtered with suction. The solids were washed with EtOAc (300 ml) and the combined filtrate plus washings were evaporated under reduced pressure to give a dark brown solid. This was stirred with petroleum ether (40-60°) (500 ml) plus EtOAc (20 ml) and filtered with suction to give a lighter brown solid which was washed with petroleum ether (40-60°) (100 ml) and air-dried to afford the title compound (25.37 g, 82%).

Workup

  1. additionthe solution was added dropwise over 2 h to
  2. temperaturea cooled
  3. additionDuring the addition the colour of the suspension
  4. temperatureto warm to room temperature
  5. stirringstirred at rt for 1 h
  6. temperatureThe mixture was cooled to 0° C.
  7. stirringwith vigorous stirring (effervescence observed)
  8. temperatureto warm to room temperature
  9. stirringstirred for 4 h
  10. filtrationfiltered with suction
  11. washThe solids were washed with EtOAc (300 ml)
  12. customthe combined filtrate plus washings were evaporated under reduced pressure
  13. customto give a dark brown solid
  14. filtrationfiltered with suction
  15. customto give a lighter brown solid which
  16. washwas washed with petroleum ether (40-60°) (100 ml)
  17. customair-dried

Sources & evidence

ORD record
ord-28e7f08f9ae94c288ce8f2824a8e4b52
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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