Phosphorus oxychloride → 1-Chlorophthalazine hydrochloride

Temperature

2.5 °C

A 3-neck 2 L round-bottomed flask was charged with phosphorous oxychloride (306 g, 2 mol. eq.) and cooled to about 0 to 5° C. To this was added 73 g of powdered phthalazinone (0.5 mol eq.). The reaction mass appeared as a suspension and was heated to about 60° C. with stirring. The progress of the reaction was monitored by HPLC. While the reaction mixture was maintained at approximately 50° C., about 65% of the phosphorous oxychloride was distilled out under vacuum. The concentrated reaction mixture was cooled to room temperature, about 375 mL of ethyl acetate was added, and then the mixture was purged with HCl gas for about 30 min.; thereafter, the mixture was cooled to a temperature of 0 to 5° C. and stirred for about one hour. The resulting pale yellow material was filtered and washed with 150 mL of cold ethyl acetate. The isolated material was 1-chlorophthalazine hydrochloride, which was dried under vacuum for about 3 hrs at 30° C. Yield =65%; purity=99%.

1. temperaturewas heated to about 60° C.
2. temperatureWhile the reaction mixture was maintained at approximately 50° C.
3. distillationabout 65% of the phosphorous oxychloride was distilled out under vacuum
4. customThe concentrated reaction mixture
5. temperaturewas cooled to room temperature
6. customthe mixture was purged with HCl gas for about 30 min.
7. temperaturethereafter, the mixture was cooled to a temperature of 0 to 5° C.
8. stirringstirred for about one hour
9. filtrationThe resulting pale yellow material was filtered
10. washwashed with 150 mL of cold ethyl acetate
11. customwas dried under vacuum for about 3 hrs at 30° C
12. customYield =65%

ORD record

ord-548bcdd2f20f48c4bbe635dd4e5100c8

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07531653B2