Ethyl chloroformate → 3-(4-Bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,3]oxazine-2,4-dione

HRID 2229531

反応式

HRID 2229531 の反応式
[OH:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N(C(C)C)CC)(C)C.Cl[C:23](OCC)=[O:24].[F:28][C:29]1[CH:36]=[C:35]([Br:37])[CH:34]=[CH:33][C:30]=1[CH2:31][NH2:32]>O1CCCC1.C(OCC)(=O)C>[Br:37][C:35]1[CH:34]=[CH:33][C:30]([CH2:31][N:32]2[C:4](=[O:6])[C:3]3[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:2]=3[O:1][C:23]2=[O:24])=[C:29]([F:28])[CH:36]=1

参加物

7

反応物 4

HCID 10928Ethyl chloroformateHCID 752314-Methoxysalicylic AcidHCID 81531Diisopropylethylamine2 回HCID 3770848(4-Bromo-2-fluorophenyl)methanamine

生成物 1

HCID 184681743-(4-Bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,3]oxazine-2,4-dione収率 36.5%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 2-hydroxy-4-methoxybenzoic acid (2.04 g, 12.2 mmol) in tetrahydrofuran (20 mL, 0.6 M) was cooled to 0° C. After being treated with diisopropylethylamine (4.4 mL, 25.3 mmol) and ethyl chloroformate (2.4 mL, 25.1 mmol), the mixture was stirred at room temperature for 1 h and subsequently treater with a solution of 2-fluoro-4-bromobenzylamine (2.92 g, 12.1 mmol) and diisopropylethylamine (4.4 mL, 25.3 mmol) in tetrahydrofuran (15 mL). After stirring at room temperature for 22 h, the reaction mixture was diluted ethyl acetate and successively washed with 2 N HCl, saturated aq NaHCO3 and saturated aq NaCl. The organic layer was dried over Na2SO4, filtered and concentrated. The crude solid was purified by recrystallization with heptane and ethyl acetate to give 3-(4-bromo-2-fluoro-benzyl)-7-methoxy benzo[e][1,3]oxazine-2,4-dione (1.68 g, 36%): 1H NMR (DMSO-d6, 300 MHz) δ 7.87 (d, J=8.4 Hz, 1H), 7.53 (dd, J1=10.5 Hz, J2=1.1 Hz, 1H), 7.33-7.34 (m, 2H), 7.03-6.99 (m, 2H), 5.02 (s, 2H), 3.87 (s, 3H).

後処理

  1. stirringAfter stirring at room temperature for 22 h
  2. washsuccessively washed with 2 N HCl, saturated aq NaHCO3 and saturated aq NaCl
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude solid was purified by recrystallization with heptane and ethyl acetate

出典と根拠

ORDレコード
ord-c748ca75ee814d998d41de1ec7b310a6
出典データセット
uspto-grants-2002_07
特許番号
US06420426B1

関連ノート

読み込み中…