Sodium Carbonate → HCID 67112253, Verbindung

HRID 2088921

Reaktionsgleichung

Reaktionsgleichung von HRID 2088921
[O:1]1[CH2:6][CH:5]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.I[C:17]1[N:18]=[C:19]([CH:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]2)[N:20]([CH2:22][CH2:23][N:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>O.C(OC)(C)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CS(C)=O>[O:1]1[CH2:6][CH:5]=[C:4]([C:17]2[N:18]=[C:19]([CH:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]3)[N:20]([CH2:22][CH2:23][N:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH:21]=2)[CH2:3][CH2:2]1

Komponenten

9

Edukt 4

HCID 10340Sodium CarbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 67112018Tert-butyl 4-[4-iodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate

Produkt 1

HCID 67112253HCID 67112253, VerbindungAusbeute 96,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 15413tert-Butyl methyl etherLösungsmittel

Versuchsvorschrift

Combine 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (19.1 g, 1.6 eq), tert-butyl 4-[4-iodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate (27 g, 56.9 mmol), sodium carbonate (120.6 g, 3.0 eq), and dimethyl sulfoxide (135 mL). Stir for five minutes. Add tri-tert-butylphosphonium tetrafluoroborate (1.7 g, 0.1 eq) and palladium(II) acetate (645.4 mg, 0.05 eq). Stir the resulting suspension at 75-80° C. under nitrogen for 45 minutes. Allow the mixture to cool to room temperature, then dilute with water (190 mL) and methyl tert-butyl ether (80 mL). Wash the aqueous layer with methyl tert-butyl ether (3×54 mL). Wash the organics with water (60 mL) and then with a 10% w/w aqueous solution of phosphoric acid (60 mL, 20 mL). Combine these aqueous layers and wash them with methyl tert-butyl ether (60 mL). Add sodium carbonate to the acidic aqueous layer to adjust the pH to 12. Wash the basic aqueous layer with methyl tert-butyl ether (120 mL, 30 mL). Wash the combined organics with aqueous saturated sodium chloride, dry over anhydrous magnesium sulfate, and concentrate in vacuo to give tert-butyl 4-[4-(3,6-dihydro-2H-pyran-4-yl)-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate (23.6 g, 96%). MS (ES) m/z=431 [M]+.

Aufarbeitung

  1. stirringStir the resulting suspension at 75-80° C. under nitrogen for 45 minutes
  2. washWash the aqueous layer with methyl tert-butyl ether (3×54 mL)
  3. washWash the organics with water (60 mL)
  4. washCombine these aqueous layers and wash them with methyl tert-butyl ether (60 mL)
  5. washWash the basic aqueous layer with methyl tert-butyl ether (120 mL, 30 mL)
  6. washWash the combined organics with aqueous saturated sodium chloride
  7. dry with materialdry over anhydrous magnesium sulfate
  8. concentrationconcentrate in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-373a90f4c0d447c08f48ebe43527dfdb
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08436002B2

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