1-Methyl-3-phenyl-1H-1,2,4-triazole → (2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl)(2-methyl-5-phenyl-2H-1,2,4-triazol-3-yl)methanol

HRID 2105084Notes

Reaction equation

[CH3:1][N:2]1[CH:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:3]1.C([Li])CCC.[F:18][C:19]1[CH:26]=[CH:25][C:24]([C:27]2([CH3:32])[O:31][CH2:30][CH2:29][O:28]2)=[CH:23][C:20]=1[CH:21]=[O:22]>C1COCC1>[F:18][C:19]1[CH:26]=[CH:25][C:24]([C:27]2([CH3:32])[O:28][CH2:29][CH2:30][O:31]2)=[CH:23][C:20]=1[CH:21]([C:6]1[N:2]([CH3:1])[N:3]=[C:4]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:5]=1)[OH:22]

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of 1-methyl-3-phenyl-1H-1,2,4-triazole (1.56 g, 9.83 mmol) in THF (50 mL) cooled to −78° C. was added 1.6 M n-butyl lithium (6.76 ml, 10.8 mmol) drop-wise and stirred for 30 min. Next a solution of Intermediate 416.2 (2.46 g, 11.8 mmol) in THF (15 mL) was added drop-wise and stirred for 5 min before allowing the mixture to warm to 23° C. The reaction mixture was quenched with aqueous NH4Cl and extracted with EtOAc (3×50 mL). The organic layer was washed with H2O, brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 100% EtOAc/hexanes gradient) to afford 3.6 g of Intermediate 416.3. 1H NMR (400 MHz, CDCl3) δ ppm 1.59 (s, 3H) 3.62 (s, 3H) 3.66-3.78 (m, 2H) 3.91-4.04 (m, 2H) 6.22 (s, 1H) 6.94-7.07 (m, 1H) 7.32-7.49 (m, 5H) 7.70 (dd, J=7.25, 2.42 Hz, 1H) 7.97-8.05 (m, 2H).

Workup

stirringstirred for 5 min
customThe reaction mixture was quenched with aqueous NH4Cl
extractionextracted with EtOAc (3×50 mL)
washThe organic layer was washed with H2O, brine
dry with materialdried (Na2SO4)
concentrationconcentrated
customThe crude product was purified by flash chromatography (0 to 100% EtOAc/hexanes gradient)

Sources & evidence

ORD record: ord-50d9bf50857d4e0fa21eea1d95c4fe67
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07576098B2

Reaction notes

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