Sulfuric Acid → HCID 131733274, compound

HRID 512122Notes

Reaction equation

HRID 512122 reaction equation
[NH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[C:4](=O)[NH:3][C:2]1=O.C[Si](C)(C)N[Si](C)(C)C.S(=O)(=O)(O)O.Br[CH2:28][C:29]1[CH:30]=[C:31]([CH:36]=[CH:37][CH:38]=1)[C:32]([O:34][CH3:35])=[O:33]>C1(C)C=CC=CC=1.O1CCOCC1.CO>[CH3:35][O:34][C:32]([C:31]1[CH:30]=[C:29]([CH:38]=[CH:37][CH:36]=1)[CH2:28][N:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[N:3][CH2:2]1)=[O:33]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 13838HexamethyldisilazaneHCID 4718725,6,7,8-Tetrahydroquinazoline-2,4(1H,3H)-dioneHCID 517981Methyl 3-(bromomethyl)benzoate

Product 1

HCID 131733274HCID 131733274, compoundYield 13%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
122.5 °C

Procedure

To a mixture of 5,6,7,8-tetrahydroquinazoline-2,4(1H, 3H)-dione (10.4 g, 62 mmol) and hexamethyldisilazane (HMDS, 33 mL, 158 mmol) in toluene (100 mL) was added concentrated sulfuric acid (0.34 mL, 6.2 mmol) at r.t. The mixture was heated to reflux overnight until a clear solution was obtained. After the removal of toluene and excess HMDS with vacuum evaporation, methyl 3-bromomethylbenzoate (16 g, 70 mmol) was added to the residue. The reaction mixture was heated to 115-130° C. and was stirred at this temperature for 4 h. The reaction mixture was diluted with 1,4-dioxane (6 mL) and methanol (100 mL) at 100° C., and was stirred for 30 min. The reaction mixture was evaporated to remove the solvent. The residue was dissolved in ethyl acetate (EA, 300 mL) and washed by 1N hydrochloric acid (100 mL×1) and water (100 mL×3). The organic layer was dried with anhydrous sodium sulfate and evaporated to give the crude product, which was purified by column chromatography on silica gel (petroleum ether: ethyl acetate=2:1) to give the title compound (2.3 g, 12% yield) as yellow powder. 1H NMR (DMSO-d6): 11.40 (s, 1H), 7.87 (d, J=7.5 Hz, 1 H), 7.79 (s, 1H), 7.55-7.44 (m, 2H), 5.12 (s, 2H), 3.85 (s, 3H), 2.45-2.35 (m, 2H ), 2.25-2.20 (m, 2H), 1.65-1.40 (m, 4H). MS: m/z 315.4 [M+H]+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight until a clear solution
  3. customwas obtained
  4. customAfter the removal of toluene and excess HMDS
  5. additionwas added to the residue
  6. stirringwas stirred for 30 min
  7. customThe reaction mixture was evaporated
  8. customto remove the solvent
  9. dissolutionThe residue was dissolved in ethyl acetate (EA, 300 mL)
  10. washwashed by 1N hydrochloric acid (100 mL×1) and water (100 mL×3)
  11. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  12. customevaporated
  13. customto give the crude product, which
  14. customwas purified by column chromatography on silica gel (petroleum ether: ethyl acetate=2:1)

Sources & evidence

ORD record
ord-5101f517e47e4a689f5a1748ffafef0c
Source dataset
uspto-grants-2015_08
Patent number
US09102631B2

Reaction notes

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