2,6-Lutidine → 2-Amino-4-ethynyl-thiophene-3-carboxylic acid ethyl ester

HRID 1244161Notes

Reaction equation

HRID 1244161 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:11]#[CH:12])=[CH:9][S:8][C:7]=1[NH:13]C(OC(C)(C)C)=O)=[O:5])[CH3:2].N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si](C(C)(C)C)(C)C)(=O)=O.[NH4+].[Cl-].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:11]#[CH:12])=[CH:9][S:8][C:7]=1[NH2:13])=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 25517Ammonium Chloride2×HCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 2724141Tetrabutylammonium FluorideHCID 865965472-t-Butoxycarbonylamino-4-ethynyl-thiophene-3-carboxylic acid ethyl ester

Product 1

HCID 860308212-Amino-4-ethynyl-thiophene-3-carboxylic acid ethyl esterYield 77.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-t-Butoxycarbonylamino-4-ethynyl-thiophene-3-carboxylic acid ethyl ester (5.86 g, 19.85 mmol) was dissolved in anhydrous CH2Cl2 (125 mL). This was treated with 2,6-lutidine (4.62 mL, 39.70 mmol) followed by dropwise addition of t-butyldimethylsilyl trifluoromethanesulfonate (6.84 mL, 29.77 mmol). This was stirred at room temperature for 2 hr. Next it was poured into sat. NH4Cl (100 mL) and then extracted with EtOAc (3×100 mL). The combined extracts were washed with H2O (1×100 mL), and brine (1×100 mL). The organic layer was dried (Na2SO4), filtered and the solvent removed in vacuo. The residue was dissolved in anhydrous THF (85 mL) and treated with tetrabutylammonium fluoride (19.85 mL, 19.85 mmol, 1 M in THF). The reaction was then stirred at room temperature for 1 hr. The reaction was poured into sat. NH4Cl (100 mL) and then extracted with EtOAc (3×100 mL). The combined extracts were washed with H2O (1×100 mL), and brine (1×100 mL). The extracts were dried (Na2SO4), filtered and the solvent removed in vacuo. The crude product was purified by flash chromatography (SiO2, 1 EtOAc/9 hexanes) to afford the title compound (3.0 g, 77%). MS m/e (CI) 196.0 (M+H)+; 1H NMR (300 MHz, CDCl3): δ ppm 1.38 (t, 2H), 3.07 (s, 1H), 4.32 (q, 2H), 6.04 (s, 2H), 6.54 (s, 1H), 7.26 (s, 1H); MS m/e (CI) 196.0 (M+H)+.

Workup

  1. extractionextracted with EtOAc (3×100 mL)
  2. washThe combined extracts were washed with H2O (1×100 mL), and brine (1×100 mL)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. dissolutionThe residue was dissolved in anhydrous THF (85 mL)
  7. stirringThe reaction was then stirred at room temperature for 1 hr
  8. extractionextracted with EtOAc (3×100 mL)
  9. washThe combined extracts were washed with H2O (1×100 mL), and brine (1×100 mL)
  10. dry with materialThe extracts were dried (Na2SO4)
  11. filtrationfiltered
  12. customthe solvent removed in vacuo
  13. customThe crude product was purified by flash chromatography (SiO2, 1 EtOAc/9 hexanes)

Sources & evidence

ORD record
ord-3454b7e8170642b889d08e7572d20473
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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