Triethylamine → Ethyl N-[6-fluoro-3-[2-(trimethylsilyl)ethynyl]-2-pyridinyl]carbamate

HRID 2425468Notes

Reaction equation

HRID 2425468 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[NH:5][C:6]1[C:11](I)=[CH:10][CH:9]=[C:8]([F:13])[N:7]=1)[CH3:2].[C:15]([Si:17]([CH3:20])([CH3:19])[CH3:18])#[CH:16].C(N(CC)CC)C.C(OCC)(=O)C>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.O>[CH2:1]([O:3][C:4](=[O:14])[NH:5][C:6]1[C:11]([C:16]#[C:15][Si:17]([CH3:20])([CH3:19])[CH3:18])=[CH:10][CH:9]=[C:8]([F:13])[N:7]=1)[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 66111TrimethylsilylacetyleneHCID 58172458Ethyl (6-fluoro-3-iodopyridin-2-yl)carbamate

Product 1

HCID 58172478Ethyl N-[6-fluoro-3-[2-(trimethylsilyl)ethynyl]-2-pyridinyl]carbamateYield 42%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of compound 57 (4 g, 12.9 mmol), 3.3 ml (23.4 mmol) TMSA (ethynyl-trimethyl-silane), 246 mg (1.29 mmol) Cu(I)iodide, 454 mg (0.65 mmol) PdCl2(PPh3)2 (454 mg, 0.64 mmol) and triethylamine (6.3 ml) was stirred and degassed (N2). The resulting reaction mixture was stirred for 10 hours at 100° C. (closed vessel), cooled and poured into ethyl acetate and H2O. The organic layer was washed with H2O, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (diethyl ether/PE (1/3)) to afford (6-fluoro-3-trimethylsilanylethynyl-pyridin-2yl)-carbamic acid ethyl ester (58) (oil, 1.5 g, 42%). 1H-NMR (200 MHz, CDCl3): δ 7.76 (bt, J=8 Hz, 1H), 7.68-7.60 (bs, 1H), 6.56 (dd, J=8 Hz, 3 Hz, 1H), 4.29 (q, J=8 Hz, 2H), 1.34 (t, J=8 Hz, 3H), 0.3 (s, 9H). (TLC diethyl ether/PE 1/1 Rf 0.39).

Workup

  1. customdegassed (N2)
  2. customThe resulting reaction mixture
  3. stirringwas stirred for 10 hours at 100° C.
  4. custom(closed vessel)
  5. temperaturecooled
  6. washThe organic layer was washed with H2O
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (diethyl ether/PE (1/3))

Sources & evidence

ORD record
ord-b11bcc493a054ccb8ef10be69b42fcdb
Source dataset
uspto-grants-2011_06
Patent number
US07964728B2

Reaction notes

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