반응 #64115

반응 방정식

triphenyl phosphite

methylene chloride

4-hydroxyquinazoline

→

4-chloroquinazoline hydrochloride

용매

pyridine

반응 조건

후처리

1. 1
   온도the mixture was cooled to -5° to 10° C
2. 2
   기타Then 3.67 Kg of chlorine gas was bubbled in over a three hour period while the temperature of the mixture
3. 3
   온도was maintained in the range of 0° to 10° C.

실험 절차

The compound of Example 2 was prepared on a larger scale, using a preferred process, as follows: To 54 L of methylene chloride, and 1.8 L of pyridine, 6.5 Kg of 4-hydroxyquinazoline was added, and the mixture was cooled to -5° to 10° C. To this mixture 15.7 Kg of triphenyl phosphite was added. Then 3.67 Kg of chlorine gas was bubbled in over a three hour period while the temperature of the mixture was maintained in the range of 0° to 10° C., to produce 4-chloroquinazoline hydrochloride. After stirring the mixture an additional hour, 105 mL of water was added to quench excess halogenating reagent. Then 9.7 Kg of 4-(t-butyl)benzeneethanol was added over a 15 minute period while the mixture was maintained at 10° to 20° C. The mixture was heated to reflux (40°-45° C.) and held at reflux for three hours. After vacuum distilling the contents of the reaction to minimize volume, 56 L of toluene was added. The contents of the reaction were again vacuum distilled, 56 L of heptane were added, and the mixture was cooled to 30°-35° C. The HCl salt of the desired product was isolated by filtration, and washed with toluene/heptane.

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