Potassium Acetate → 5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole

HRID 538990Notes

Reaction equation

HRID 538990 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[CH:11][N:10]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:9]=2)=[CH:4][CH:3]=1.Br[C:22]1[CH:27]=[CH:26][C:25]([C:28]2[N:32]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[N:31]=[CH:30][N:29]=2)=[CH:24][CH:23]=1.C([O-])(=O)C.[K+].[CH3:46][C:47]1([CH3:63])[C:51]([CH3:53])([CH3:52])[O:50][B:49]([B:54]2[O:58][C:57]([CH3:60])([CH3:59])[C:56]([CH3:62])([CH3:61])[O:55]2)[O:48]1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH3:46][C:47]1([CH3:63])[C:51]([CH3:53])([CH3:52])[O:50][B:49]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[N:12]=[CH:11][N:10]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:9]=3)=[CH:4][CH:3]=2)[O:48]1.[CH3:60][C:57]1([CH3:59])[C:56]([CH3:61])([CH3:62])[O:55][B:54]([C:22]2[CH:23]=[CH:24][C:25]([C:28]3[N:32]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[N:31]=[CH:30][N:29]=3)=[CH:26][CH:27]=2)[O:58]1

Participants

8

Reactant 4

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 595259995-(4-bromophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazoleHCID 595262653-(4-bromophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole

Product 2

HCID 595255703-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazoleHCID 680888445-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazoleYield 98%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

In a sealed tube, a mixture of 3-(4-bromophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole and 5-(4-bromophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (5.00 g, 14.1 mmol), DPPF (0.469 g, 0.847 mmol), PdCl2dppf-dichloromethane (1.38 g, 1.69 mmol), potassium acetate (4.15 g, 42.3 mmol) and 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (7.17 g, 28.2 mmol) in dioxane (141 mL) was heated at 90° C. under N2 for 18 hours. The crude product was filtered through a pad of Celite, washed with saturated NaHCO3, brine, dried over MgSO4, filtered, and concentrated. Purification of the crude material by column chromatography, eluting with 0-30% EtOAc/Hexanes, afforded 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole and 5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (5.55 g, 98%) as a mixture of two regioisomers. LCMS (APCI+) m/z 402 [M+H]+.

Workup

  1. filtrationThe crude product was filtered through a pad of Celite
  2. washwashed with saturated NaHCO3, brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the crude material by column chromatography
  7. washeluting with 0-30% EtOAc/Hexanes

Sources & evidence

ORD record
ord-8fe734810f74453ca4058948523960ef
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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