Methyl acetoacetate → 1-(2-chloro-4-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid

Temperature

5 °C

To crude 1-azido-2-chloro-4-cyclopropylbenzene (0.2 M solution in THF) was added methyl 3-oxobutanoate (146 g, 1254 mmol) and the resulting mixture was cooled to 5° C. NaOMe (232 mL, 1254 mmol) was added slowly forming a precipitate and the mixture was stirred at RT for 64 hrs. The resulting suspension was cooled in an ice bath and water (2 L) was added. The mixture was transferred to a separating funnel and the aqueous layer was extracted with Me-THF (500 mL). The aqueous layer was acidified with 2M HCl (aq) and extracted with EtOAc (2 L) (1×) and (1 L) (2×). The combined organic extracts were washed with water (1 L) and brine (1 L), dried over Na2SO4, filtered and concentrated under reduced pressure to give an orange oily residue. Water (300 mL) was added and the mixture was stirred for 30 min, filtered, washed with water and dried under reduced pressure to give the title compound as orange crystals.

1. customforming a precipitate
2. temperatureThe resulting suspension was cooled in an ice bath
3. customThe mixture was transferred to a separating funnel
4. extractionthe aqueous layer was extracted with Me-THF (500 mL)
5. extractionextracted with EtOAc (2 L) (1×) and (1 L) (2×)
6. washThe combined organic extracts were washed with water (1 L) and brine (1 L)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto give an orange oily residue
11. stirringthe mixture was stirred for 30 min
12. filtrationfiltered
13. washwashed with water
14. customdried under reduced pressure

ORD record

ord-0daaa5bf1664488aa6a6e10108403771

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403833B2