Phenol → 6-Iodo4-phenoxyquinazoline

HRID 1264048Notes

Reaction equation

[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[I:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2Cl>CN(C=O)C>[I:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2[O:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A suspension of NaH (washed free of mineral oil) in DMF (40 mL) was cooled to 0° C. and a solution of phenol (5.65 g, 60 mmol) in DMF (20 mL) was added dropwise. Upon completion of addition, 6-iodo-4-chloroquinazoline (14.6 g, 50.3 mmol) was added as a solid in small portions. The cooling bath was moved and the reaction mixture was stirred at room temperature for 2 hours. The mixture was then quenched with water (200 mL), diluted with EtOAc (300 mL) and transferred to a separatory funnel. The organic layer was washed with dilute aqueous NaOH, water and brine and dried over Na2SO4. Filtration of the solids and removal of the solvent provided quinazoline 13 (17.2 g, 98%) as a yellow solid. 1H NMR (400 MHz; CDCl3): δ 8.74 (d, 1H), 8.14 (s, 1H), 8.12 (dd, 1H), 7.71 (d, 1H), 7.49 (dd, 2H), 7.32 (t, 1H), 7.22 (m, 2H).

Workup

additionwas added as a solid in small portions
customThe mixture was then quenched with water (200 mL)
additiondiluted with EtOAc (300 mL)
customtransferred to a separatory funnel
washThe organic layer was washed with dilute aqueous NaOH, water and brine
dry with materialdried over Na2SO4
filtrationFiltration of the solids and removal of the solvent

Sources & evidence

ORD record: ord-224dc04c709946cbabd3dbad3c1d276b
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06541481B2

Reaction notes

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