Binap, (A+-)- → 4-{4-[2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-phenyl]-piperazine-1-carboxylic acid benzyl ester

HRID 1185707

Reaktionsgleichung

Reaktionsgleichung von HRID 1185707
[CH3:1][O:2][C:3](=[O:36])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[N:17]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:18]([C:21]2[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:37]([N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1)([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:40]([O:39][C:37]([N:47]1[CH2:52][CH2:51][N:50]([C:24]2[CH:25]=[CH:26][C:21]([C:18]3[N:17]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:16]([CH:12]4[CH2:13][CH2:14][CH2:15][N:11]4[C:9](=[O:10])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:36])[CH:6]([CH3:8])[CH3:7])=[N:20][CH:19]=3)=[CH:22][CH:23]=2)[CH2:49][CH2:48]1)=[O:38])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Komponenten

7

Edukt 4

HCID 634876Binap, (A+-)-HCID 643495Benzyl piperazine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 66620156(1-{2-[5-(4-bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl)-carbamic acid methyl ester

Produkt 1

HCID 666202604-{4-[2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-phenyl]-piperazine-1-carboxylic acid benzyl esterAusbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

(1-{2-[5-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (1033 mg, 1.8 mmol) and 4-Cbz-piperazine (588 mg, 2.7 mmol) in toluene (9 mL) were treated with Pd(OAc)2 (20 mg, 0.09 mmol), BINAP (110 mg, 0.1 mmol), and NaOtBu (428 mg, 4.45 mmol). The mixture was stirred in a sealed tube at 110° C. for 18 hours. The solution was concentrated, diluted with EtOAc (50 mL), and washed with saturated NaHCO3 (20 mL), H2O (20 mL), and brine (20 mL). The solution was dried over MgSO4 and subjected to a 120 g SiO2 COMBIFLASH column (0-100% EtOAc-hexanes gradient) to afford 4-{4-[2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-phenyl]-piperazine-1-carboxylic acid benzyl ester (166 mg, 13%): MS (ESI) m/z 719 [M+H]+.

Aufarbeitung

  1. concentrationThe solution was concentrated
  2. additiondiluted with EtOAc (50 mL)
  3. washwashed with saturated NaHCO3 (20 mL), H2O (20 mL), and brine (20 mL)
  4. dry with materialThe solution was dried over MgSO4

Quellen und Nachweise

ORD-Eintrag
ord-5977f00ecb8542d7b086219e7b67c19b
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669234B2

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