1,4-Dioxane → 3-(4-bromo-2-prop-1-yn-1-yl-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole

HRID 2282277Notes

Reaction equation

HRID 2282277 reaction equation
Br[C:2]1[S:3][C:4]([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)=[C:5]([Br:7])[N:6]=1.[Cl-].[Li+].O1CCOCC1.[CH2:29]([Sn](CCCC)(CCCC)C#CC)[CH2:30][CH2:31]C>C(Cl)Cl.[Cu]I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O.CCCCCC>[Br:7][C:5]1[N:6]=[C:2]([C:29]#[C:30][CH3:31])[S:3][C:4]=1[C:8]1[N:12]=[CH:11][N:10]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:9]=1

Participants

9

Reactant 4

HCID 312751,4-DioxaneHCID 433294Lithium ChlorideHCID 2733165Tributyl(prop-1-yn-1-yl)stannaneHCID 580950363-(2,4-dibromo-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole

Product 1

HCID 580949523-(4-bromo-2-prop-1-yn-1-yl-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazoleYield 76.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-(2,4-dibromo-1,3-thiazol-5-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazole (6.00 g, 13.6 mmol), Lithium chloride (1.73 g, 40.9 mmol), Copper(I) iodide (0.779 g, 4.09 mmol) and Tetrakis(triphenylphosphine)platinum (0) (0.848 g, 0.681 mmol) in anhydrous 1,4-Dioxane (120 mL, 1500 mmol) was sonicated under Argon atmosphere for 2 minutes in a 250 mL RBF. Tributyl(1-propynyl)tin (4.80 mL, 15.0 mmol) was added. The mixture was heated to 100° C. for 1 hour under Argon atmosphere. The mixture was cooled to r.t., diluted with DCM (˜150 mL), filtered through Celite, and washed with DCM. The filtrate was rotavaped to give a crude residue. Chromatograph in a 330 g ISCO column using EtOAc/hexane (0/100 to 50/50) gave a pure solid product (4.14 g, 76% yield). LCMS: (FA) ES+ 399, 401. 1H NMR (400 MHz, d1-chloroform) δ 8.29 (s, 1H), 5.54 (s, 2H), 3.69-3.74 (m, 2H), 2.15 (s, 3H), 0.93-0.97 (m, 2H), 0.00 (s, 9H).

Workup

  1. customwas sonicated under Argon atmosphere for 2 minutes in a 250 mL RBF
  2. temperatureThe mixture was cooled to r.t.
  3. filtrationfiltered through Celite
  4. washwashed with DCM
  5. customto give a crude residue

Sources & evidence

ORD record
ord-133daeee229d48d2bac5b3affc562919
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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