Sodium hydride → tert-Butyl 4-hydroxy-6-iodo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate

HRID 905895Notes

Reaction equation

HRID 905895 reaction equation
[C:1]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])(=[O:6])[CH2:2][C:3]([O-])=[O:4].[H-].[Na+].[I:14][C:15]1[CH:27]=[CH:26][C:18]2[N:19](C)[C:20](=O)[O:21][C:22](=O)[C:17]=2[CH:16]=1>O1CCOCC1>[OH:21][C:22]1[C:17]2[C:18](=[CH:26][CH:27]=[C:15]([I:14])[CH:16]=2)[N:19]([CH3:20])[C:3](=[O:4])[C:2]=1[C:1]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 21883978Tert-butyl malonateHCID 538260965-iodo-N-methylisatoic anhydride

Product 1

HCID 59340042tert-Butyl 4-hydroxy-6-iodo-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of tert-butyl malonate (5 ml, 20 mmol) in 1,4-Dioxane (70 ml) was added 60% Sodium hydride (0.8 g, 35 mmol) in portions. The mixture was stirred at room temperature for 45 min. then a solution of 6-iodo-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (6.1 g, 20 mmol) in 1,4-Dioxane (40 ml) was added. The mixture was placed in an oil bath at 60° C. and the bath temp was raised to 120° C. over a period of 20 min after which stirring was continued for 90 min. The solvent was removed on a roto-evaporator and cold water (300 ml) was added to the residue. The mixture was washed with DCM (100 ml) then the aqueous phase was acidified with 2N HCl. The organic layer was extracted into DCM (2×100 ml) and after drying over MgSO4 the solvent was removed on a roto-evaporator. Yield=4.1 g.

Workup

  1. customThe mixture was placed in an oil bath at 60° C.
  2. temperaturethe bath temp was raised to 120° C. over a period of 20 min after which
  3. stirringstirring
  4. waitwas continued for 90 min
  5. customThe solvent was removed on a roto-evaporator and cold water (300 ml)
  6. additionwas added to the residue
  7. washThe mixture was washed with DCM (100 ml)
  8. extractionThe organic layer was extracted into DCM (2×100 ml)
  9. dry with materialafter drying over MgSO4 the solvent
  10. customwas removed on a roto-evaporator

Sources & evidence

ORD record
ord-295adb5238ed4d8484a97cb204dafc82
Source dataset
uspto-grants-2011_09
Patent number
US08012968B2

Reaction notes

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