Sodium Bicarbonate → 1-methylethyl {(2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate

HRID 2041724Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2041724
[CH3:1][O:2][C:3]1[CH:4]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH3:20][CH:21]([O:23][C:24](=[O:41])[NH:25][C@H:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33](Br)[CH:34]=2)[N:29]([C:37](=[O:39])[CH3:38])[C@@H:28]([CH3:40])[CH2:27]1)[CH3:22].C([O-])(O)=O.[Na+]>C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.C(Cl)Cl.O1CCOCC1>[C:37]([N:29]1[C:30]2[C:35](=[CH:34][C:33]([C:5]3[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)=[CH:32][CH:31]=2)[C@H:26]([NH:25][C:24](=[O:41])[O:23][CH:21]([CH3:20])[CH3:22])[CH2:27][C@@H:28]1[CH3:40])(=[O:39])[CH3:38]

Komponenten

7

Edukt 3

HCID 516892Sodium BicarbonateHCID 159061952-(3,4-Dimethoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Produkt 1

HCID 681848671-methylethyl {(2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamateAusbeute 56,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 18456801dichloropalladium DCMKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A flask was charged with 2-[3,4-bis(methyloxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.429 g, 1.625 mmol), 1-methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 100) (0.5 g, 1.354 mmol), a saturated NaHCO3 aqueous solution (1.5 mL, 1.354 mmol) and bis(diphenylphosphino)ferrocene]dichloropalladium(II)-DCM adduct (0.111 g, 0.135 mmol) then filled with 1,4-dioxane (7 mL). The resulting mixture was degassed by bubbling nitrogen in to it, stirred at 100° C. for 1 hr under microwave irradiation then cooled to room temperature. The reaction mixture was filtered through celite and concentrated in vacuovacuo. The residue was partitioned between EtOAC (30 mL) and water (30 mL) and the layers were separated. The organic phase was washed with brine (25 mL) dried over MgSO4 and concentrated in vacuovacuo. Purification of the residue by flash chromatography on silica gel (gradient:0 to 60% AcOEt in Hexanes) gave 1-methylethyl {(2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (327 mg, 0.766 mmol, 56.6%).

Aufarbeitung

  1. customThe resulting mixture was degassed
  2. customby bubbling nitrogen in to it
  3. temperaturethen cooled to room temperature
  4. filtrationThe reaction mixture was filtered through celite and
  5. concentrationconcentrated in vacuovacuo
  6. customThe residue was partitioned between EtOAC (30 mL) and water (30 mL)
  7. customthe layers were separated
  8. washThe organic phase was washed with brine (25 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuovacuo
  11. customPurification of the residue by flash chromatography on silica gel (gradient:0 to 60% AcOEt in Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-487ca02fe4634298978e427de2e8b45d
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08580957B2

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