Hydrochloric Acid → HCID 59340073, compound

HRID 905897Notes

Reaction equation

HRID 905897 reaction equation
[C:1]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:13])[CH2:2][C:3]([O:5]CC1C=CC=CC=1)=O.[H-].[Na+].[CH3:24][N:25]1[C:30]2[CH:31]=[C:32]([C:35]([O:37][CH3:38])=[O:36])[CH:33]=[CH:34][C:29]=2[C:28](=O)[O:27]C1=O.Cl>CN(C=O)C.CCOC(C)=O>[OH:27][C:28]1[C:29]2[C:30](=[CH:31][C:32]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:34]=2)[N:25]([CH3:24])[C:3](=[O:5])[C:2]=1[C:1]([O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:13]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 84754Dibenzyl malonateHCID 12511618HCID 12511618, compound

Product 1

HCID 59340073HCID 59340073, compoundYield 6.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of dibenzyl malonate (2.99 ml, 11.9 mmol) in DMF (41 ml) was added sodium hydride in portions. The cloudy grey mixture was stirred at room temperature for 20 min after which time a clear solution resulted. The solution was further stirred at 120° C. for 20 min before adding a solution of methyl 1-methyl-2,4-dioxo-2,4-dihydro-1H-benzo[d][1,3]oxazine-7-carboxylate (2.82 g, 11.9 mmol) in DMF (41 ml). The resulting yellow solution was stirred at 120° C. for 3 hrs. The reaction mixture was cooled to room temperature, 2N HCl and EtOAc were added and the layers were separated. The aqueous layer was extracted with EtOAc 3×, the combined organics were washed with H2O (1×) followed by sat. NaCl (2×). The organic phase was then dried over MgSO4, filtered and concentrated to give a yellow solid. Purification was performed by ISCO using 10% to 50% Hex/EtOAc gradient, 40 g column to give 300 mg of a yellow solid.

Workup

  1. customresulted
  2. stirringThe solution was further stirred at 120° C. for 20 min
  3. stirringThe resulting yellow solution was stirred at 120° C. for 3 hrs
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc 3×
  7. washthe combined organics were washed with H2O (1×)
  8. dry with materialThe organic phase was then dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a yellow solid
  12. customPurification

Sources & evidence

ORD record
ord-7ec5da7724d84c4ebcc68e7ef566edb3
Source dataset
uspto-grants-2011_09
Patent number
US08012968B2

Reaction notes

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