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

HRID 457942

반응식

HRID 457942 반응식
[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

참가 물질

7

반응물 4

HCID 10928Ethyl chloroformateHCID 752314-Methoxysalicylic AcidHCID 81531Diisopropylethylamine2회HCID 3770848(4-Bromo-2-fluorophenyl)methanamine

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

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 treated 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][1,31 oxazine-2,4-dione (1.68 g, 36%): 1H NMR (DMSO-d6, 300 MHz) δ 7.87 (d, J=8.4 Hz, 1 H), 7.53 (dd, J1=10.5 Hz, J2=1.1 Hz, 1 H), 7.33–7.34 (m, 2 H), 7.03–6.99 (m, 2 H), 5.02 (s, 2 H), 3.87 (s, 3 H).

후처리

  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

출처 및 근거

ORD 기록
ord-dc8a6168e7e541e286a4605e93058656
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07189749B2

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