Sodium Hydroxide → 3-Phenyl-5-(2-thienyl)-1,2,4-oxadiazole

Temperature

70 °C

A solution of benzamide oxime (24.92%) in 2-methyl THF (67.53 g, 124 mmoles) was charged to a 500 mL flask, followed by DI water (20.0 g), 55% aqueous tetrabutylammonium hydroxide (0.94 g), and 50% sodium hydroxide (0.96 g, 12 mmoles). To this mixture was added 2-thiophenecarbonyl chloride (17.77 g, 120 mmoles) and 50% sodium hydroxide (9.60 g, 120 mmoles) simultaneously over 30 minutes while heating to about 70° C. The reaction was complete is less than one hour. The temperature was reduced to 60° C., and the pH of the aqueous phase was neutralized to 7.61, and was drained off to waste. A hot solution of 1.25 g of Morwet D-425 in 100 ml DI water was added to the mixture, and the 2-phase mixture was heated to distill off the 2-methyltetrahydrofuran/water azeotrope (boiling point 71° C.). Additional water (150 ml) was pumped into the reactor flask over about 15 minutes, once the 2-methyltetrahydrofuran began to distill out. While maintaining good agitation, the pot temperature reached 100.5° C. (vapor temperature 97° C.). The slurry was cooled and filtered using a coarse glass frit. The scale was scraped off the agitator and combined with the wet cake; the scale was only about 3% of total product. The combined wet cake was washed with hot DI water (3×50 ml) and suction-dried for 5 minutes to give a 3-phenyl-5-(thiophen-2-yl)-1,2,4-oxadiazole wet cake, 34.80 g. The loss on drying of the wet cake was 20.13%. The assay of the dried 3-phenyl-5-(thiophen-2-yl)-1,2,4-oxadiazole was 96.12%, and the residual chloride was <200 ppm.

1. waitThe reaction was complete is less than one hour
2. customwas reduced to 60° C.
3. temperaturethe 2-phase mixture was heated
4. distillationto distill off the 2-methyltetrahydrofuran/water
5. distillationto distill out
6. temperatureWhile maintaining good agitation
7. customreached 100.5° C.
8. custom(vapor temperature 97° C.)
9. temperatureThe slurry was cooled
10. filtrationfiltered
11. washThe combined wet cake was washed with hot DI water (3×50 ml)
12. customsuction-dried for 5 minutes

ORD record

ord-6026aa6b494c4ee58293c261e88f169b

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273037B2