Ethyl Acetate → 2-(1-Bromoethyl)3-(4-fluorophenyl)-3H-quinazolin-4-one

HRID 1827327노트

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HRID 1827327 반응식
[CH2:1]([C:3]1[N:12]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[C:11](=[O:20])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1)[CH3:2].C([O-])(=O)C.[Na+].[Br:26]Br.C(OCC)(=O)C>C(O)(=O)C.CCCCCC.O>[Br:26][CH:1]([C:3]1[N:12]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[C:11](=[O:20])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1)[CH3:2]

참가 물질

8

반응물 4

HCID 8857Ethyl AcetateHCID 24408Bromine2회HCID 517045Sodium AcetateHCID 120180582-Ethyl-3-(4-fluorophenyl)-3H-quinazolin-4-one2회

생성물 1

HCID 120180572-(1-Bromoethyl)3-(4-fluorophenyl)-3H-quinazolin-4-one수율 96.1%

시약·촉매·용매 3

HCID 176Acetic Acid용매2회HCID 962Water용매HCID 8058Hexane용매

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온도
40 °C

실험 절차

To a solution of 7.084 g 2-ethyl-3-(4-fluorophenyl)-3H-quinazoline-4-one (IV) (26.40 mmol, 1.000 equiv) and 2.60 g sodium acetate (31.7 mmol, 1.20 equiv) dissolved in 30 mL glacial acetic acid at 40° C. (external temperature; oil bath) was added dropwise by addition funnel a solution of 1.36 mL bromine (26.4 mmol, 1.00 equiv) in 5 mL glacial acetic acid over 60 min. Upon completed addition of the bromine solution, the reaction was stirred an additional 60 min, after which time TLC indicated no IV remained (Rf=0.44; 40% ethyl acetate in hexane) and the heterogeneous mixture was poured into 400 mL water. The resulting aqueous, acidic mixture, with precipitate, was stirred vigorously at ambient temperature for two h. The precipitate was collected by vacuum filtration, rinsing with warm (ca. 40° C.) water (2×50 mL) and cold isopropyl alcohol (50 mL). The solid was dried in vacuo over phosphorous pentoxide overnight, affording 8.81 g of a white solid.m.p. 179.8° C. 1H NMR (CDCl3) δ 2.06 (d, J=0.016p, 3H), 4.55 (q, 0.016 p, 2H), 7.16 (ddd, 1H, J1=2.4 Hz, J2=4.8 Hz, J3=8.4 Hz), 7.24 (dt, 1H, J1=2.8 Hz, J2=8.0 Hz), 7.28 (dt, 1H, J1=2.8 Hz, J2=8.4 Hz), 7.51–7.58 (m, 2H), 7.80–7.81 (m, 2H), 8.28 (dt, 1H, J1=0.8 Hz, J2=8.0 Hz) ppm. MS (ESI+) 348.0 [MH]+.

후처리

  1. stirringThe resulting aqueous, acidic mixture, with precipitate, was stirred vigorously at ambient temperature for two h
  2. filtrationThe precipitate was collected by vacuum filtration
  3. washrinsing
  4. dry with materialThe solid was dried in vacuo over phosphorous pentoxide overnight

출처 및 근거

ORD 기록
ord-f796d6f26f7448b395d2041ff60af79d
출처 데이터셋
uspto-grants-2006_05
특허 번호
US07053215B2

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