Potassium Carbonate → N-Boc-pyrrolidine

HRID 71839

Reaktionsgleichung

Reaktionsgleichung von HRID 71839
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1C1NC(C2C=CC(C3C4C(=C(B5OC(C)(C)C(C)(C)O5)C=CC=4)C=CC=3)=CC=2)=CN=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N1CCCC1C1NC(Br)=CN=1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 56605248tert-Butyl 2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 666210752-(5-{4-[5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-1-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 643455N-Boc-pyrrolidineAusbeute 87,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

2-(5-{4-[5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-1-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (159 mg, 0.281 mmol), 2-(5-Bromo-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (178 mg (0.562 mmol), Pd(PPh3)4 (65 mg, 0.0562 mmol) and K2CO3 (0.281 mL of a 2 M aqueous solution, 0.562 mmol) were combined in 1,2-dimethoxyethane (3 mL) and degassed with bubbling N2 for 12 min. The mixture was then heated to 85° C. for 22 hours then cooled to RT, diluted with ethyl acetate (50 mL) and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated. The crude residue was purified by silica column chromatography (80% to 100% EtOAc/hexanes) to afford 2-(5-{4-[5-(1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester)-naphthalen-1-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (42 mg, 22%).

Aufarbeitung

  1. customdegassed with bubbling N2 for 12 min
  2. temperaturethen cooled to RT
  3. additiondiluted with ethyl acetate (50 mL)
  4. washwashed with water and brine
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe crude residue was purified by silica column chromatography (80% to 100% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-d4f4637b843d4aa48bae86feb58e3754
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822430B2

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