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

HRID 569822
ノート
印刷プレビュー

反応式

HRID 569822 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

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 ether 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).

後処理

  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 ether acetate (0.9 l) and n-hexane (0.9 l)

出典と根拠

ORDレコード
ord-8f5bad4139074fcca6b0a27d3af9181a
出典データセット
uspto-grants-1988_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US04734419

反応ノート

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