Thiazole → Methyl 4-(thiazol-2-Yl)benzoate

HRID 14097

Reaction equation

HRID 14097 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.I[C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=1>O1CCCC1.C(OCC)C.[Cl-].[Zn+2].[Cl-]>[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=1

Participants

7

Reactant 3

HCID 9256ThiazoleHCID 69273Methyl 4-iodobenzoateHCID 178418339Butyllithium

Product 1

HCID 11241445Methyl 4-(thiazol-2-Yl)benzoate

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a −70° C., stirred solution of thiazole (270 μL, 3.8 mmol) in tetrahydrofuran (10 mL) is added n-butyl lithium (2.6 mL of a 1.6 M solution in hexanes, 4.2 mmol). After 30 min, zinc chloride (11.4 mL of a 1.0 M solution in diethyl ether, 11.4 mmol) is added. The reaction mixture is warmed to 0° C. and methyl 4-iodobenzoate (1 g, 3.8 mmol) and palladium(0)tetrakis(triphenylphosphine) (530 mg, 0.4 mmol) are added. The reaction mixture is heated at 70° C. for 20 h under argon, cooled to room temperature, and then partitioned between ethyl acetate and water. The organic layer is washed with water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (3:1 hexanes/ethyl acetate) yields the title compound. 1H NMR (300 MHz, CDCl3) δ 8.14-8.03 (m, 4H), 7.93-7.92 (m, 1H), 7.42-7.41 (m, 1H), 3.95 (s, 3H).

Workup

  1. temperatureThe reaction mixture is heated at 70° C. for 20 h under argon
  2. temperaturecooled to room temperature
  3. custompartitioned between ethyl acetate and water
  4. washThe organic layer is washed with water, and brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (3:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-e541d94b30ea431c80f9c1c2b868d2fd
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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