2-Bromothiazole → 2-(1-ethoxymethyl-1H-imidazol-2-yl)-thiazole

HRID 586368Notes

Reaction equation

HRID 586368 reaction equation
[CH2:1]([O:3][CH2:4][N:5]1[CH:9]=[CH:8][N:7]=[C:6]1[Sn](CCCC)(CCCC)CCCC)[CH3:2].Br[C:24]1[S:25][CH:26]=[CH:27][N:28]=1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][CH2:4][N:5]1[CH:9]=[CH:8][N:7]=[C:6]1[C:24]1[S:25][CH:26]=[CH:27][N:28]=1)[CH3:2]

Participants

6

Reactant 3

HCID 764302-BromothiazoleHCID 516892Sodium BicarbonateHCID 222603931-ethoxymethyl-2-tributylstannanyl-1H-imidazole

Product 1

HCID 222603972-(1-ethoxymethyl-1H-imidazol-2-yl)-thiazoleYield 26%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A solution of crude 1-ethoxymethyl-2-tributylstannanyl-1H-imidazole (previous example), 2-bromothiazole (1.05 mL, 11.6 mmol, 1.0 equivalents based on integration of 1H NMR of crude 1-ethoxymethyl-2-tributylstannanyl-1H-imidazole), and Pd(PPh3)4 (0.67 g, 0.58 mmol) in toluene (20 mL) is stirred at 80° C. for 18 hours. After cooling to room temperature, the reaction mixture is poured into saturated aqueous NaHCO3 and extracted twice with CH2Cl2. The combined extracts are dried over Na2SO4 and concentrated in vacuo. The residue is purified by flash chromatography on silica gel, eluting with 2:1 hexanes:EtOAc (+0.5% Et3N). Fractions containing product are concentrated and subjected again to flash chromatography on silica gel. Elution with 2:1 hexanes:EtOAc (+0.5% Et3N) affords (26%) of 2-(1-ethoxymethyl-1H-imidazol-2-yl)-thiazole as a bright yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J=3.2 Hz, 1H), 7.33 (d, J=3.2 Hz, 1H), 7.20 (d, J=1.2 Hz, 1H), 7.15 (d, J=1.2 H, 1H), 6.03 (s, 2H), 3.56 (q, J=7.2 Hz, 2H), 1.17 (t, J=7.2 Hz, 3H) ppm.

Workup

  1. customis stirred at 80° C. for 18 hours
  2. extractionextracted twice with CH2Cl2
  3. dry with materialThe combined extracts are dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by flash chromatography on silica gel
  6. washeluting with 2:1 hexanes
  7. additionFractions containing product
  8. concentrationare concentrated
  9. washElution with 2:1 hexanes

Sources & evidence

ORD record
ord-557debfb3dcc4f3d975215950a704133
Source dataset
uspto-grants-2005_08
Patent number
US06936617B2

Reaction notes

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