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

HRID 1594064Notes

Reaction equation

HRID 1594064 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.FC1C=C(C2N(CC3NC4C=NC=CC=4N3CC)C=CN=2)C=CC=1.C([O-])(O)=O.[Na+]>C1(C)C=CC=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 4

HCID 764302-BromothiazoleHCID 516892Sodium BicarbonateHCID 222603931-ethoxymethyl-2-tributylstannanyl-1H-imidazoleHCID 223801792-{[2-(3-Fluorophenyl)-1H-imidazol-1-yl]methyl}-1-ethyl-3H-imidazo[4,5-c]pyridine

Product 1

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

Reagents, catalysts & solvents 1

HCID 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-214fcef773d44b8980bb3a99afb40fb1
Source dataset
uspto-grants-2007_11
Patent number
US07300945B2

Reaction notes

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