Water → tert-Butyl (2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)acetate

HRID 472756Notes

Reaction equation

HRID 472756 reaction equation
[C:1]([O:5][C:6](=[O:18])[CH2:7][NH:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[NH2:16])([CH3:4])([CH3:3])[CH3:2].Cl[C:20](Cl)([O:22]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.O>C(Cl)Cl.CCCC(C)C>[C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:9](=[O:17])[C:10]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:16][C:20]1=[O:22])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 94429TriphosgeneHCID 53432551tert-Butyl N-(2-aminobenzoyl)glycinate

Product 1

HCID 53432550tert-Butyl (2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)acetate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 78922-MethylpentaneSolvent

Procedure

To a cooled (<5° C.) solution of (2-amino-benzoylamino)-acetic acid tert-butyl ester (33 g, 0.132 mol) in DCM (200 ml), a solution of triphosgene (14.08 g, 0.047 mol) in DCM (70 ml) is added dropwise over 30 minutes, keeping the temperature below 5° C. The resulting white/cream precipitate is treated dropwise with triethylamine (21 ml, 0.145 mol), keeping the temperature of the reaction below 5° C. The bright yellow reaction mixture is gradually allowed to warm to RT and stirred overnight. Water (250 ml) is added to the reaction mixture with stirring. Mixture is partitioned and the aqueous phase is washed with DCM (100 ml). The organic extracts are combined, washed with NaHCO3 (2×200 ml), water (2×150 ml), brine (200 ml), and concentrated in vacuo to give a pale orange solid. This is then slurried in isohexane for 30 minutes, filtered, then taken up in DCM (90 ml) with heating. The solution is then placed in the fridge over the weekend. The crystalline material formed is filtered and washed with a minimal amount of cold DCM to afford the title compound.

Workup

  1. customthe temperature below 5° C
  2. customthe temperature of the reaction below 5° C
  3. stirringwith stirring
  4. customMixture is partitioned
  5. washthe aqueous phase is washed with DCM (100 ml)
  6. washwashed with NaHCO3 (2×200 ml), water (2×150 ml), brine (200 ml)
  7. concentrationconcentrated in vacuo
  8. customto give a pale orange solid
  9. filtrationfiltered
  10. temperaturewith heating
  11. customThe crystalline material formed
  12. filtrationis filtered
  13. washwashed with a minimal amount of cold DCM

Sources & evidence

ORD record
ord-76ff42df1c524f6089b2d70531a7b5c9
Source dataset
uspto-grants-2014_01
Patent number
US08633211B2

Reaction notes

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