Phenol → 6-Iodo4-phenoxyquinazoline

HRID 991464Notes

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 13 (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 6-iodo4-phenoxyquinazoline 14 (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-8bec783f936d45178bb432dec0c0a0c8
Source dataset: uspto-grants-2002_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06465449B1

Reaction notes

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