Sodium hydride → Ethyl 6-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

HRID 601898Notes

Reaction equation

HRID 601898 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:8]2[NH:9][C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:11][C:7]=2[CH2:6][CH2:5]1.[CH3:17][Si:18]([CH2:21][CH2:22][O:23][CH2:24]Cl)([CH3:20])[CH3:19]>CN(C=O)C>[O:3]=[C:4]1[C:8]2[N:9]([CH2:24][O:23][CH2:22][CH2:21][Si:18]([CH3:20])([CH3:19])[CH3:17])[C:10]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:11][C:7]=2[CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 57659859Ethyl 6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

Product 1

HCID 59180143Ethyl 6-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylateYield 89.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To sodium hydride (60% dispersion in mineral oil) (0.46 g, 11.4 mmol, 1.1 equiv) in anhydrous DMF (10 mL) under a nitrogen atmosphere at 0° C. was added dropwise a solution ethyl 6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (2.0 g, 10 mmol, 1 equiv) in anhydrous DMF (15 mL). After stirring for 30 min at 0° C., SEM-Cl (2.1 g, 12.4 mmol, 1.2 equiv) was then added dropwise over 5 min and the mixture warmed to rt overnight. The reaction was quenched by pouring the reaction contents into a beaker of ice water. It was extracted with EtOAc (4×50 mL) and the combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography (0-30% EtOAc/heptane) to afford 2.9 g of ethyl 6-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (86% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 6.84 (s, 1H), 5.87 (s, 2H), 4.35 (q, J=7.13 Hz, 2H), 3.57 (dd, J=8.59, 7.71 Hz, 2H), 2.82-2.92 (m, 4H), 1.38 (t, J=7.14 Hz, 3H), 0.85-0.92 (m, 2H), −0.05 (s, 9H).

Workup

  1. temperaturethe mixture warmed to rt overnight
  2. customThe reaction was quenched
  3. additionby pouring
  4. customthe reaction contents into a beaker of ice water
  5. extractionIt was extracted with EtOAc (4×50 mL)
  6. washthe combined organic extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by flash chromatography (0-30% EtOAc/heptane)

Sources & evidence

ORD record
ord-820e9d10b5bc4deb97695188956eac84
Source dataset
uspto-grants-2011_03
Patent number
US07902252B2

Reaction notes

Loading…