Toluene → 6-iodo-4-(tetrahydro-2H-pyran-2-yloxy)quinazoline

HRID 533698Notes

Reaction equation

[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[OH:12].C1(C)C=CC=CC=1.FC(F)(F)C(O)=O.[O:27]1[CH:32]=[CH:31][CH2:30][CH2:29][CH2:28]1>CCCCCC.C(OCC)(=O)C>[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[O:12][CH:28]1[CH2:29][CH2:30][CH2:31][CH2:32][O:27]1

Participants

Conditions

Temperature: 112.5 °C

Procedure

In a 4-neck glass flask provided with a mechanical stirrer, condenser and thermometer 30 g of 6-iodoquinazoline-4-ol (110 mmoles), 300 mL of toluene dried on molecular sieves, 1.26 g (0.84 mL) of trifluoroacetic acid (0.1 mol. equiv.) and 79.4 g (80 mL) of 3,4-dihydro-2H-pyran (DHP) (944 mmoles; 8.6 mol. equiv.) were introduced, under nitrogen. Stirring was carried out to reflux (T=110-115° C.) for 2-3 hours and the reaction was controlled under TLC with Hexane/Ethyl Acetate (2:8) eluent. Upon completing the reaction a homogeneous solution was obtained which was cooled to ambient temperature and washed using 2×120 mL of saturated solution of sodium chloride. The organic phase was concentrated under vacuum to 40-45° C. ext T up to residue.

Workup

customIn a 4-neck glass flask provided with a mechanical stirrer, condenser
additionwere introduced, under nitrogen
customthe reaction a homogeneous solution
customwas obtained which
temperaturewas cooled to ambient temperature
washwashed
concentrationThe organic phase was concentrated under vacuum to 40-45° C. ext T up to residue

Sources & evidence

ORD record: ord-ef00a5b85aa34759b5e8a16f8587e8cb
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853396B2

Reaction notes

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