Methanol → Ethyl (7-chloro-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)acetate

HRID 1699095Notes

Reaction equation

HRID 1699095 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:13])[NH:7][C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.C[Si](C)(C)N[Si](C)(C)C.[C:23]([O:26][CH2:27][CH3:28])(=[O:25])[CH3:24].CO>C1(C)C=CC=CC=1.S(=O)(=O)(O)O>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:13])[NH:7][C:8](=[O:12])[N:9]2[CH2:24][C:23]([O:26][CH2:27][CH3:28])=[O:25])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 13838HexamethyldisilazaneHCID 2468587-Chloroquinazoline-2,4-diol

Product 1

HCID 9838691Ethyl (7-chloro-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)acetate

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidCatalystHCID 1140TolueneSolvent

Procedure

To a mixed suspension of 7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazoline (20 g) and hexamethyldisilazane (16.42 g) in toluene (60 ml) was added sulfuric acid (0.80 g) dropwise and the silylation reaction was carried out at an internal temperature of 110˜120° C. for 6 hours. After completion of silylation, the toluene was distilled off to recover a concentrate containing 7-chloro-2,4-bis(trimethylsilyloxy)quinazoline. To this concentrate were added propylene carbonate (40 ml), ethyl chloroacetate (13.72 g) and ethyl bromoacetate (3.40 g), and the reaction was carried out at an internal temperature of 125˜140° C. for 6 hours. After completion of reaction, the reaction mixture was cooled to an internal temperature of ≦70° C. and ethyl acetate (80 ml) was added. Then, methanol (60 ml) was added dropwise over 30 minuets. After completion of dropwise addition, the mixture was cooled to ≦20° C. and stirred for 1 hour. The resulting crystal crop was harvested by filtration, washed serially with methanol (40 ml) and water (100 ml) and dried to provide ethyl 2-(7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-1-yl)acetate (28.16 g) as white crystals.

Workup

  1. customthe silylation reaction
  2. distillationAfter completion of silylation, the toluene was distilled off
  3. customto recover a concentrate
  4. additioncontaining 7-chloro-2,4-bis(trimethylsilyloxy)quinazoline
  5. additionTo this concentrate were added propylene carbonate (40 ml), ethyl chloroacetate (13.72 g) and ethyl bromoacetate (3.40 g)
  6. waitthe reaction was carried out at an internal temperature of 125˜140° C. for 6 hours
  7. customAfter completion of reaction
  8. additionwas added
  9. additionAfter completion of dropwise addition
  10. temperaturethe mixture was cooled to ≦20° C.
  11. filtrationThe resulting crystal crop was harvested by filtration
  12. washwashed serially with methanol (40 ml) and water (100 ml)
  13. customdried

Sources & evidence

ORD record
ord-b1819d7d97f4490cb77baca645d139da
Source dataset
uspto-grants-2002_02
Patent number
US06344559B1

Reaction notes

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