Sodium Carbonate → Ethyl 4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)benzoate

HRID 1255177

Reaktionsgleichung

Reaktionsgleichung von HRID 1255177
[CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]2)[O:3][CH2:2]1.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.[CH2:44]([O:46][C:47]([C:49]1[CH:54]=[CH:53][C:52](B(O)O)=[CH:51][CH:50]=1)=[O:48])[CH3:45].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.C(#N)C>[O:3]1[C:4]2([CH2:9][CH2:8][C:7]([C:52]3[CH:53]=[CH:54][C:49]([C:47]([O:46][CH2:44][CH3:45])=[O:48])=[CH:50][CH:51]=3)=[CH:6][CH2:5]2)[O:11][CH2:1][CH2:2]1

Komponenten

8

Edukt 5

HCID 10340Sodium CarbonateHCID 388544N-(5-chloropyridin-2-yl)-1,1,1-trifluoro-N-trifluoromethanesulfonylmethanesulfonamideHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 2733832Lithium HexamethyldisilazideHCID 27343504-Ethoxycarbonylphenylboronic acid

Produkt 1

HCID 67159072Ethyl 4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)benzoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a cooled (−78° C.) solution of 1,4-cyclohexanedione mono-ethylene ketal (1.00 g, 6.40 mmol) in anhydrous THF (30 mL) was added lithium bis(trimethylsilyl)amide (7.7 mL, 1.0 M in THF, 7.70 mmol) dropwise. After 10 min, a solution of 2-[N,N-bis(trifluoromethylsulfonyl)amino]5-chloropyridine (2.51 g, 6.40 mmol) in THF (10 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 sat. aq. NaHCO3. The mixture was extracted with EtOAc. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated in vacuo. To a flask containing the unpurified enol triflate (1.36 g, 4.72 mmol) were added 4-ethoxycarbonylphenylboronic acid (1.10 g, 5.66 mmol) and trans-dichlorobis(triphenylphosphine) palladium (II) (331 mg, 0.472 mmol). Acetonitrile (24 mL) and sodium carbonate (11.8 mL, 1.0 M aqueous, 11.8 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 ambient 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 30% EtOAc in hexanes, then 30 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 289.1 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.97 (d, J=8.5 Hz, 2H), 7.44 (d, J=8.5 Hz, 2H), 6.12-6.10 (m, 1H), 4.36 (q, J=7.0 Hz, 2H), 4.03 (s, 4H), 2.70-2.67 (m, 2H), 2.50-2.48 (m, 2H), 1.93 (t, J=6.5 Hz, 2H), 1.39 (t, J=7.0 Hz, 3H).

Aufarbeitung

  1. customwas quenched
  2. additionby pouring into sat. aq. NaHCO3
  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. customthe resulting mixture was degassed via nitrogen
  8. customsparge
  9. temperatureto cool to ambient temperature
  10. additionwas poured into water
  11. extractionThe mixture was extracted with EtOAc
  12. concentrationthe organic phase was concentrated in vacuo
  13. customPurification by chromatography on silica gel (0 to 30% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-988e7bebda5c40a9a5ef1e3c06847d50
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08455638B2

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