Dimethylformamide → 4-(2-Fluorophenyl)-1-methyl-1H-1,2,3-triazole-5-carbaldehyde

To a pre cooled (−70° C. to −78° C.) solution of 4-(2-fluorophenyl)-1-methyl-1H-1,2,3-triazole 3 (51 g, 287.84 mmol) under nitrogen atmosphere in THF (1200 ml) was added n-Butyllithium (138.16 ml, 345.41 mmol, 2.5M solution in hexane) and stirred for 2 h. Then DMF (1200 ml, 14794.844 mmol) was added and stirred at −78° C. for 30 min. The reaction was monitored by TLC and UPLC. The reaction mixture was slowly quenched with ice cold water (1000 ml) and the aqueous layer was extracted with ethyl acetate (5×1000 ml). The combined organic layer was dried over sodium sulphate, filtered and concentrated to afford crude mass (50 g, 84.66% mass balance). It was purified by gravity column using 20% ethyl acetate in pet ether as an eluent to afford desired product 4-(2-Fluorophenyl)-1-methyl-1H-1,2,3-triazole-5-carbaldehyde (40 g, 67.72%) as reddish solid. Then it was triturated with methyl tert-butyl ether (1000 ml) and hexane (500 ml), the supernant layer was decanted and the solid was dried to furnish desired product 4-(2-Fluorophenyl)-1-methyl-1H-1,2,3-triazole-5-carbaldehyde (32 g, 54.18% yield) as white solid.

1. stirringstirred at −78° C. for 30 min
2. customThe reaction mixture was slowly quenched with ice cold water (1000 ml)
3. extractionthe aqueous layer was extracted with ethyl acetate (5×1000 ml)
4. dry with materialThe combined organic layer was dried over sodium sulphate
5. filtrationfiltered
6. concentrationconcentrated
7. customto afford crude mass (50 g, 84.66% mass balance)
8. customIt was purified by gravity column

ORD record

ord-06d326762c5e40d4b8ac28fe8f0f1c50

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206160B2