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

HRID 1007159Notes

Reaction equation

HRID 1007159 reaction equation
[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]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 24408Bromine2×HCID 517045Sodium AcetateHCID 120180582-Ethyl-3-(4-fluorophenyl)-3H-quinazolin-4-one2×

Product 1

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

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 962WaterSolventHCID 8058HexaneSolvent

Conditions

Temperature
40 °C

Procedure

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) δ2.06 (d, J=0.016p, 3H), 4.55 (q, 0.016p, 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]+.

Workup

  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

Sources & evidence

ORD record
ord-74d2492834cb43c28716d3b4965f1b2d
Source dataset
uspto-grants-2004_09
Patent number
US06794379B2

Reaction notes

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