Chlorotrimethylsilane → 3-(3-Chlorophenyl)-2-(difluoromethoxy)-5-(pyridin-2-ylmethyl)pyridine

HRID 578838Notes

Reaction equation

[Br-].[Cl:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]([CH2:19][Zn+])[CH:12]=[N:13][C:14]=2[O:15][CH:16]([F:18])[F:17])[CH:6]=[CH:7][CH:8]=1.BrCCBr.C[Si](Cl)(C)C.BrC[C:32]1[CH:33]=[C:34](C2C=CC=C(Cl)C=2)[C:35](OC(F)F)=[N:36][CH:37]=1>C1COCC1.[Zn]>[Cl:2][C:3]1[CH:4]=[C:5]([C:9]2[C:14]([O:15][CH:16]([F:18])[F:17])=[N:13][CH:12]=[C:11]([CH2:19][C:35]3[CH:34]=[CH:33][CH:32]=[CH:37][N:36]=3)[CH:10]=2)[CH:6]=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 70 °C

Procedure

((5-(3-Chlorophenyl)-6-(difluoromethoxy)pyridin-3-yl)methyl)zinc(II) bromide. To a suspension of zinc (42.77 mg, 0.65 mmol) in THF (1 mL) was added 1,2-dibromoethane (2.48 μL, 0.03 mmol). The resulting mixture was heated at 70° C. for 10 minutes before being cooled to room temperature. Once cooled, trimethylsilylchloride (2.92 μL, 0.02 mmol) was added and the solution was stirred at room temperature for an additional 30 min. To the activated zinc solution was added 5-(bromomethyl)-3-(3-chlorophenyl)-2-(difluoromethoxy)pyridine (Intermediate 12, 200 mg, 0.57 mmol) and the resulting mixture was heated at 70° C. for 8 h. The reaction mixture was cooled to room temperature and decanted from the solids to afford a ˜0.5 M solution of the title compound.

Workup

temperaturebefore being cooled to room temperature
temperatureOnce cooled
temperaturethe resulting mixture was heated at 70° C. for 8 h
temperatureThe reaction mixture was cooled to room temperature
customdecanted from the solids

Sources & evidence

ORD record: ord-26fb6478e7e44ad89dd4782a5c12977a
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040692B2

Reaction notes

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