Trimethylsilylacetylene → Ethyl 2-ethynyl-4-methylthiazole-5-carboxylate

HRID 2381774Notes

Reaction equation

HRID 2381774 reaction equation
Br[C:2]1[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([CH3:7])[N:6]=1.[CH:13](N(CC)C(C)C)(C)[CH3:14].C[Si](C#C)(C)C>C1(C)C=CC=CC=1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:13]([C:2]1[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([CH3:7])[N:6]=1)#[CH:14]

Participants

7

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 2824057Ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate

Product 1

HCID 59179676Ethyl 2-ethynyl-4-methylthiazole-5-carboxylateYield 79.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of ethyl 2-bromo-4-methylthiazole-5-carboxylate (0.50 g, 2.00 mmol) in anhydrous toluene (5 mL) was added copper(I) iodide (0.008 g, 0.040 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.028 g, 0.040 mmol) and N,N-diisopropylethylamine (0.52 mL, 3.00 mmol). The reaction mixture was degassed and the reaction flask was flashed and filled with nitrogen followed by the addition of trimethylsilylacetylene (0.42 mL, 3.00 mmol). The reaction mixture was heated at 40° C. for 5 hours, cooled to ambient temperature, poured onto a silica gel pad and eluted with hexanes and hexanes/ethyl acetate (10/1). The collections were concentrated in vacuo and the obtained clear oil was dissolved in dichloromethane (5 mL) and treated with 10% aqueous sodium hydroxide (0.5 mL) at ambient temperature for 1 hour. The reaction mixture was diluted with dichloromethane (15 mL), washed with water (7 mL) and brine (7 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford the title compound as a yellowish solid (0.31 g, 77%): 1H NMR (300 MHz, CDCl3) δ 4.24 (q, J=7.1 Hz, 2H), 3.53 (s, 1H), 2.63 (s, 3H), 1.27 (t, J=7.1 Hz, 3H); MS (ES+) m/z 196.2 (M+1).

Workup

  1. customThe reaction mixture was degassed
  2. additionfilled with nitrogen
  3. temperaturecooled to ambient temperature
  4. additionpoured onto a silica gel pad
  5. washeluted with hexanes and hexanes/ethyl acetate (10/1)
  6. concentrationThe collections were concentrated in vacuo
  7. dissolutionthe obtained clear oil was dissolved in dichloromethane (5 mL)
  8. additiontreated with 10% aqueous sodium hydroxide (0.5 mL) at ambient temperature for 1 hour
  9. additionThe reaction mixture was diluted with dichloromethane (15 mL)
  10. washwashed with water (7 mL) and brine (7 mL)
  11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a66d95749c934cdd8b7d2dae639207ee
Source dataset
uspto-grants-2012_09
Patent number
US08258160B2

Reaction notes

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