Nitrogen → 5-(4-fluorophenyl)-2-methyl-2H-tetrazole

Temperatur

82 °C

A mixture of 5-(4-fluorophenyl)-2H-tetrazole (6.61 g, 40.3 mmol), K2CO3 (6.68 g, 48.3 mmol), and iodomethane (3.02 mL, 48.3 mmol) in acetonitrile (115 mL) was heated to reflux (ca. 82° C.) for one hour. After cooling, the mixture was concentrated to dryness and the residue was partitioned between water (75 mL) and EtOAc (100 mL). The layers were separated, the aqueous layer was back-extracted with EtOAc (50 mL) and the combined organic layers were washed with water (50 mL) and brine (50 mL). The organic layer was dried over anh. MgSO4, filtered and concentrated to give 9.5 g as a colorless oil that solidified upon standing. The residue was purified by flash chromatography to give 2 main products: Intermediate 35B as the N2 isomer: 5-(4-fluorophenyl)-2-methyl-2H-tetrazole (5.09 g, 70.9% yield) as a white solid: No NOE observed between the methyl group at 4.42 ppm and the aromatic protons; 1H NMR (400 MHz, DMSO-d6) δ ppm 4.42 (s, 3H) 7.33-7.45 (m, 2H) 8.03-8.14 (m, 2H); MS m/z 179.2 (M+H)+; HPLC >99.5%, RT=1.75 minutes.

1. temperaturewas heated
2. temperatureAfter cooling
3. concentrationthe mixture was concentrated to dryness
4. customthe residue was partitioned between water (75 mL) and EtOAc (100 mL)
5. customThe layers were separated
6. extractionthe aqueous layer was back-extracted with EtOAc (50 mL)
7. washthe combined organic layers were washed with water (50 mL) and brine (50 mL)
8. dry with materialThe organic layer was dried over anh. MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto give 9.5 g as a colorless oil that
12. customThe residue was purified by flash chromatography
13. customto give 2 main products

ORD-Eintrag

ord-06ea726513df4ed4843357b3bc99f71d

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09409906B2