1,2-Dimethoxyethane → [1-(2-{5-[4'-(2-tert-butoxycarbonylamino-acetyl)-biphenyl-4-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

HRID 2038996Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2038996
[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=1)=[O:10])([CH3:4])([CH3:3])[CH3:2].[CH3:19][O:20][C:21](=[O:54])[NH:22][CH:23]([C:27]([N:29]1[CH2:33][CH2:32][CH2:31][CH:30]1[C:34]1[NH:35][C:36]([C:39]2[CH:44]=[CH:43][C:42](B3OC(C)(C)C(C)(C)O3)=[CH:41][CH:40]=2)=[CH:37][N:38]=1)=[O:28])[CH:24]([CH3:26])[CH3:25].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.O>[CH3:19][O:20][C:21](=[O:54])[NH:22][CH:23]([C:27]([N:29]1[CH2:33][CH2:32][CH2:31][CH:30]1[C:34]1[NH:35][C:36]([C:39]2[CH:40]=[CH:41][C:42]([C:14]3[CH:15]=[CH:16][C:11]([C:9](=[O:10])[CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:18])=[CH:12][CH:13]=3)=[CH:43][CH:44]=2)=[CH:37][N:38]=1)=[O:28])[CH:24]([CH3:26])[CH3:25]

Komponenten

7

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 59610197tert-butyl N-[2-(4-bromophenyl)-2-oxoethyl]carbamateHCID 66619939[2-Methyl-1-(2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester

Produkt 1

HCID 66620939[1-(2-{5-[4'-(2-tert-butoxycarbonylamino-acetyl)-biphenyl-4-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl esterAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of [2-(4-Bromo-phenyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester (1 g, 3.2 mmol), [2-methyl-1-(2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (1.57 g, 3.2 mmol), tetrakis(triphenylphosphine)palladium(0) (183 mg, 0.15 mmol), potassium carbonate (878 mg, 6.5 mmol), 1,2-dimethoxyethane (25 mL) and water (2.5 mL) was stirred at 80° C. for 16 hours. The mixture was cooled and all volatiles were removed under reduced pressure. The resulting residue was taken up in dichloromethane (100 mL) and washed with water (25 mL) and saturated sodium chloride (25 mL). The organic phase was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was subjected to flash chromatography with eluent of (10% methanol in ethyl acetate) and hexane. The product-containing fractions were combined and the solvent was removed under reduced pressure to provide [1-(2-{5-[4′-(2-tert-butoxycarbonylamino-acetyl)-biphenyl-4-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (869 mg, 1.4 mmol, 44%).

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. customall volatiles were removed under reduced pressure
  3. washwashed with water (25 mL) and saturated sodium chloride (25 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. customThe solvent was removed under reduced pressure
  7. customthe solvent was removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-d1f536e3123b427fa1a3d3bf0e258538
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08575118B2

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