Phosphorus oxychloride → 4-Chloro-8-methylquinazoline
Reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][NH:8][C:7]2=O.O=P(Cl)(Cl)[Cl:15]>>[Cl:15][C:7]1[C:6]2[C:11](=[C:2]([CH3:1])[CH:3]=[CH:4][CH:5]=2)[N:10]=[CH:9][N:8]=1Participants
Conditions
- Temperature
- 120 °C
Procedure
POCl3 (300 mL) was taken in a 2 L round bottom flask under nitrogen. To this was added 8-Methylquinazolin-4(3H)-one (45 g) in portions. The reaction mixture refluxed at 120° C. for 12 h. Reaction completion was monitored by TLC and LCMS. After completion, the reaction mixture was cooled to RT and evaporated to dryness under reduced pressure. The resulted residue was dissolved in DCM (500 mL) and quenched slowly into an ice cold solution of saturated K2CO3 with constant stirring. Then the organic layer was separated and washed with brine solution, dried over sodium sulphate and concentrated under vacuum to afford (45 g, 90% yield) of the titled compound as yellow solid. This was taken for next step without further purification. 1H NMR (CDCl3, 400 MHz) δ 9.03 (s, 1H), 8.08-8.06 (dd, J=8.9, 8.4 Hz, 1H), 7.77-7.76 (d, J=7.1 Hz, 1H), 7.59-7.56 (d, J=15.5 Hz, 1H), 2.75 (s, 3H).
Workup
- customReaction completion
- temperatureAfter completion, the reaction mixture was cooled to RT
- customevaporated to dryness under reduced pressure
- dissolutionThe resulted residue was dissolved in DCM (500 mL)
- customquenched slowly into an ice cold solution of saturated K2CO3 with constant stirring
- customThen the organic layer was separated
- washwashed with brine solution
- dry with materialdried over sodium sulphate
- concentrationconcentrated under vacuum
Sources & evidence
- ORD record
- ord-d5852c598a3741d497ced2811c7cf705
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09139568B2
Reaction notes
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