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

HRID 1988720Notes

Reaction equation

HRID 1988720 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 experimental), 2-bromothiazole (1.05 mL, 11.6 mmol, 1.0 eq 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 h. 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 resubjected 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 Hz, 1H), 6.03 (s, 2H), 3.56 (q, J=7.2 Hz, 2H), 1.17 (t, J=7.2 Hz, 3H) ppm.

Workup

  1. extractionextracted twice with CH2Cl2
  2. dry with materialThe combined extracts are dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue is purified by flash chromatography on silica gel
  5. washeluting with 2:1 hexanes-EtOAc (+0.5% Et3N)
  6. additionFractions containing product
  7. concentrationare concentrated
  8. washElution with 2:1 hexanes-EtOAc (+0.5% Et3N)

Sources & evidence

ORD record
ord-fa954a65f6f347a3bc4a462ae5d604c2
Source dataset
uspto-grants-2010_01
Patent number
US07642267B2

Reaction notes

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