Sodium Carbonate → tert-Butyl 3-[4-(ethoxycarbonyl)phenyl]-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 1891227Notes

Reaction equation

HRID 1891227 reaction equation
[C:1]([N:8]1[CH2:12][CH2:11][C:10](=O)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].FC(F)(F)S(N(C1C=CC(Cl)=CN=1)S(C(F)(F)F)(=O)=O)(=O)=O.[CH2:46]([O:48][C:49]([C:51]1[CH:56]=[CH:55][C:54](B(O)O)=[CH:53][CH:52]=1)=[O:50])[CH3:47].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.C(#N)C>[CH2:46]([O:48][C:49]([C:51]1[CH:56]=[CH:55][C:54]([C:10]2[CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:12][CH:11]=2)=[CH:53][CH:52]=1)=[O:50])[CH3:47]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 388544N-(5-chloropyridin-2-yl)-1,1,1-trifluoro-N-trifluoromethanesulfonylmethanesulfonamideHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 2733832Lithium HexamethyldisilazideHCID 27343504-Ethoxycarbonylphenylboronic acid

Product 1

HCID 86644576tert-Butyl 3-[4-(ethoxycarbonyl)phenyl]-2,5-dihydro-1H-pyrrole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (−78° C.) solution of 1-Boc-3-pyrollidinone (8.00 grams, 43.2 mmol) in anhydrous THF (70 mL) was added lithium bis(trimethylsilyl)amide (49.7 mL, 1.0 M in THF, 49.7 mmol) dropwise. After 45 min, a solution of 2-[N,N-bis(trifluoromethylsulfonyl)amino]5-chloropyridine (17.81 g, 45.4 mmol) in THF (65 mL) was added, and the resulting mixture was allowed to warm slowly to ambient temperature overnight, at which point it was quenched by pouring into brine. The mixture was extracted with EtOAc. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting enol triflate was filtered though silica gel, concentrated in vacuo, and used without further purification. To a flask containing the enol triflate obtained above (4.94 g, 15.6 mmol) were added 4-ethoxycarbonylphenylboronic acid (3.32 g, 17.1 mmol) and trans-dichlorobis(triphenylphosphine) palladium (II) (1.09 g, 1.56 mmol). Acetonitrile (78 mL) and sodium carbonate (39 mL, 1.0 M aqueous, 39 mmol) were added, and the resulting mixture was degassed via nitrogen sparge. The reaction mixture was stirred at 70° C. for 3 h, then was allowed to cool to room temperature and was poured into water. The mixture was extracted with EtOAc, and the organic phase was concentrated in vacuo. Purification by chromatography on silica gel (0 to 25% EtOAc in hexanes, then 25 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 261.9 [M-t-Boc]+; 1H NMR (500 MHz, CDCl3) δ 8.03 (d, J=8.0 Hz, 2 H), 7.44 (d, J=8.5 Hz, 2H), 6.29 (ddd, J=25.0, 4, 4 Hz, 1H), 4.58-4.46 (m, 2H), 4.41-4.28 (m, 2H), 4.38 (q, J=7.0 Hz, 2H), 1.53 and 1.51 (s, doubled (rotamers) 9H), 1.40 (t, doubled (rotamers) J=7.0 Hz, 1.5H), 1.39 (t, doubled (rotamers) J=7.0 Hz, 1.5H).

Workup

  1. customwas quenched
  2. additionby pouring into brine
  3. extractionThe mixture was extracted with EtOAc
  4. customThe organic phase was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. filtrationThe resulting enol triflate was filtered though silica gel
  8. concentrationconcentrated in vacuo
  9. customused without further purification
  10. additionTo a flask containing the enol triflate
  11. customobtained above (4.94 g, 15.6 mmol)
  12. customthe resulting mixture was degassed via nitrogen
  13. customsparge
  14. temperatureto cool to room temperature
  15. additionwas poured into water
  16. extractionThe mixture was extracted with EtOAc
  17. concentrationthe organic phase was concentrated in vacuo
  18. customPurification by chromatography on silica gel (0 to 25% EtOAc in hexanes

Sources & evidence

ORD record
ord-7744247ca6e644ad9772fb1a5a0ec6ee
Source dataset
uspto-grants-2013_08
Patent number
US08507512B2

Reaction notes

Loading…