Hydrochloric Acid → Ethyl {3-[(4-bromo-2-fluorophenyl)methyl]-7-chloro-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}acetate

HRID 1639310Notes

Reaction equation

HRID 1639310 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:19])[NH:7][C:8](=[O:18])[N:9]2[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:4][CH:3]=1.[H-].[Na+].[Br:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Br)=[C:25]([F:31])[CH:24]=1.Cl>CN(C)C=O>[Br:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][N:7]2[C:6](=[O:19])[C:5]3[C:10](=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:9]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]2=[O:18])=[C:25]([F:31])[CH:24]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 27336604-Bromo-2-fluorobenzyl bromideHCID 9838691Ethyl (7-chloro-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)acetate

Product 1

HCID 11431340Ethyl {3-[(4-bromo-2-fluorophenyl)methyl]-7-chloro-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl}acetateYield 85.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of ethyl 2-(7-chloro-1,2,3,4-tetrahydro-2,4-dioxoquinazolin-1-yl)acetate (176 g) in N,N-dimethylformamide (3.5 l) was added sodium hydride (60% in mineral oil, 32.3 g) at 0° C. and the mixture was stirred at room temperature for 4 hours. To the reaction mixture was added a solution of 4-bromo-2-fluorobenzyl bromide (200 g) in N,N-dimethylformamide (100 ml) below 20° C. over a 20-minute period and the resulting mixture was stirred at room temperature for 1 hour. 3N Aqueous hydrochloric acid (62.2 ml) was added to the mixture below 15° C. and the solvent was evaporated in vacuo. The residue was poured into a mixture of ethyl acetate (3 l) and water (3 l), and the resulting mixture was stirred for 15 minutes. The precipitates were filtered off and the organic layer was separated. The solution was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was crystallized with addition of isopropyl ether and the crystals were collected by filtration and washed with isopropyl ether. The crude crystals and the precipitates were mixed and recrystallized from a mixture of ethyl acetate (0.9 l) and n-hexane (0.9 l) to give ethyl 2-[3-(4-bromo-2-fluorobenzyl)-7-chloro-1,2,3,4-tetrahydro-2,4-dioxoquinazolin-1-yl)acetate (251 g).

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 1 hour
  2. customthe solvent was evaporated in vacuo
  3. additionThe residue was poured into a mixture of ethyl acetate (3 l) and water (3 l)
  4. stirringthe resulting mixture was stirred for 15 minutes
  5. filtrationThe precipitates were filtered off
  6. customthe organic layer was separated
  7. washThe solution was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customevaporated in vacuo
  10. customThe residue was crystallized with addition of isopropyl ether
  11. filtrationthe crystals were collected by filtration
  12. washwashed with isopropyl ether
  13. additionThe crude crystals and the precipitates were mixed
  14. customrecrystallized from a mixture of ethyl acetate (0.9 l) and n-hexane (0.9 l)

Sources & evidence

ORD record
ord-3250bd95e8ba4f1da3de5fcd78b254a4
Source dataset
uspto-grants-1989_11
Patent number
US04883800

Reaction notes

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