Hydrochloric Acid → [3-(dimethylamino)phenyl](1-methyl-1H-tetrazol-5-yl)methanone

Temperature

0 °C

To a stirred solution of 1-methyl-1H-tetrazole (4.54 g, 54 mmol) in anhydrous THF (200 mL), cooled to 0° C. with a brine/ice bath, was added dropwise a solution of isopropylmagnesium chloride (2 M in THF, 27 mL, 54 mmol). After the addition was over, the resulting cloudy suspension was stirred for 15 min at 0° C. A solution of 3-(dimethylamino)-N-methoxy-N-methylbenzamide (9.37 g, 45 mmol) in THF (80 mL) was then added dropwise while keeping the internal temperature below 5° C. The reaction mixture was then allowed to warm up and stirred at room temperature for 1 h. A mixture of ice-cold water (50 mL) and aq. HCl (1 M, 55 mL) was added to the reaction mixture, the layers were separated, the water phase was extracted with ethyl acetate (3×50 mL) and the combined organic layers were dried. Purification on silica gel followed by recrystallization from diethyl ether afforded [3-(dimethylamino)phenyl](1-methyl-1H-tetrazol-5-yl)methanone as a bright yellow solid [3.06 g, yield 25%; HPLC/MS m/z=232 (M+H); logP(HCOOH)=2.21].

1. additionAfter the addition
2. customthe internal temperature below 5° C
3. temperatureto warm up
4. stirringstirred at room temperature for 1 h
5. additionwas added to the reaction mixture
6. customthe layers were separated
7. extractionthe water phase was extracted with ethyl acetate (3×50 mL)
8. customthe combined organic layers were dried
9. customPurification on silica gel
10. customfollowed by recrystallization from diethyl ether

ORD record

ord-2f8f93513122458e92b3ba02f6aeba23

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08466176B2